Materiały źródłowe

• #1 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #2 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] Then, we discuss the latest findings related to the pathogenesis of RSV. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #3 Pathogenesis of Respiratory Syncytial Virus Infection

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W2084916825

  Respiratory syncytial virus (RSV) is recognized as the most important cause of serious lower respiratory tract illness in infants and young children worldwide causing repeat infections throughout life with serious complications occurring in the elderly and immune compromised patient. […] The level of disease pathogenesis associated with RSV infection is balanced between virus elimination and the nature of the immune response to infection. […] However, significant progress has been made in understanding the virushost relationship and mechanisms associated with disease pathogenesis. […] This review summarizes important aspects of these findings, and provides current perspective on processes that may contribute to RSV disease pathogenesis.

• #4 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 m in length. The virion consists of nine structural proteins. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion. RSV can be divided into two subtypes, A and B, based on variations in the G protein. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity.

• #5 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 m in length. The virion consists of nine structural proteins. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion. RSV can be divided into two subtypes, A and B, based on variations in the G protein. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity.

• #6 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 m in length. The virion consists of nine structural proteins. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion. RSV can be divided into two subtypes, A and B, based on variations in the G protein. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity.

• #7 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 m in length. The virion consists of nine structural proteins. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion. RSV can be divided into two subtypes, A and B, based on variations in the G protein. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity.

• #8 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  Respiratory syncytial virus (RSV) is classified as a member of the genus Pneumovirus in the family Pneumoviridae. The viral genome consists of a linear, single-stranded, negative-sense, non-segmented RNA (~15.2 kb). RSV lacks haemagglutinin and neuraminidase activity. Virus particles are enveloped and pleomorphic, occurring as irregular spherical particles that are 100 to 350 nm in diameter, and as long filamentous fibres that are 60 to 200 nm in diameter and 10 m in length. The virion consists of nine structural proteins. Three proteins are associated with the nucleocapsid and include nucleoprotein (N), phosphoprotein (P), and polymerase or large protein (L). The other six viral proteins are contained within the virus envelope and include nonglycosylated matrix protein (M), M2 (M2-1 and M2-2), fusion protein (F), glycoprotein (G), and short hydrophobic protein (SH). There are two non-structural proteins, NS-1 and NS-2, which are involved in innate immune response evasion. RSV can be divided into two subtypes, A and B, based on variations in the G protein. The predominance of these subtypes alternates during different epidemic seasons however there is no difference in severity.

• #9 Respiratory Syncytial Virus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971488-overview

  Reinfection with RSV occurs at all ages; however, with recurrent infection and increasing age, RSV infections are more likely to be limited to the upper respiratory tract. […] RSV URTI is more severe than the common cold, as evidenced by the 7- to 10-day duration of illness and by the finding from one study of adults with RSV that the mean absence from work is 6 days. Studies have also demonstrated severe RSV disease in elderly persons.

• #10 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/respiratory-syncytial-virus/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. […]

• #11 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. Two important glycoproteins are involved in this RSV mechanism of action: the attachment glycoprotein (G) and the fusion glycoprotein (F), which mediate viral cell entry. Along with mediating cell entry, glycoprotein F triggers the merging of adjacent cells, giving rise to large multinucleated structures called syncytia, which cause epithelial lesions in the upper respiratory tract. Progression to the lower respiratory tract is common.

• #12 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  RSV preferentially infects the apical, but not basolateral, surface of the airway epithelial cells. […] RSV seems to specifically target luminal columnar cells after they have developed cilia. […] RSV is also shed from the apical surface, and the beating of the cilia may facilitate spreading of the infection to neighboring ciliated cells. […] RSV expresses two nonstructural (NS) proteins, NS1 and NS2, which reduce the induction of the type I IFNs, IFN-1, IFN-2, and IFN-3. […] These results suggest there is a link between the NS1 and NS2 inhibition of the host cytokine response and the ability to control viral replication. […] Autopsy studies of children who die of RSV bronchiolitis reveal that the inflammation generated by the immune response may be an important pathogenic factor, and that airway obstruction is an important component of the disease.

• #13 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  RSV preferentially infects the apical, but not basolateral, surface of the airway epithelial cells. […] RSV seems to specifically target luminal columnar cells after they have developed cilia. […] RSV is also shed from the apical surface, and the beating of the cilia may facilitate spreading of the infection to neighboring ciliated cells. […] RSV expresses two nonstructural (NS) proteins, NS1 and NS2, which reduce the induction of the type I IFNs, IFN-1, IFN-2, and IFN-3. […] These results suggest there is a link between the NS1 and NS2 inhibition of the host cytokine response and the ability to control viral replication. […] Autopsy studies of children who die of RSV bronchiolitis reveal that the inflammation generated by the immune response may be an important pathogenic factor, and that airway obstruction is an important component of the disease.

• #14 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. Two important glycoproteins are involved in this RSV mechanism of action: the attachment glycoprotein (G) and the fusion glycoprotein (F), which mediate viral cell entry. Along with mediating cell entry, glycoprotein F triggers the merging of adjacent cells, giving rise to large multinucleated structures called syncytia, which cause epithelial lesions in the upper respiratory tract. Progression to the lower respiratory tract is common.

• #15 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. Two important glycoproteins are involved in this RSV mechanism of action: the attachment glycoprotein (G) and the fusion glycoprotein (F), which mediate viral cell entry. Along with mediating cell entry, glycoprotein F triggers the merging of adjacent cells, giving rise to large multinucleated structures called syncytia, which cause epithelial lesions in the upper respiratory tract. Progression to the lower respiratory tract is common.

• #16 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #17 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #18 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] The main cell to be infected by RSV is the respiratory epithelial cell (AEC). […] In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway.

• #19 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. Two important glycoproteins are involved in this RSV mechanism of action: the attachment glycoprotein (G) and the fusion glycoprotein (F), which mediate viral cell entry. Along with mediating cell entry, glycoprotein F triggers the merging of adjacent cells, giving rise to large multinucleated structures called syncytia, which cause epithelial lesions in the upper respiratory tract. Progression to the lower respiratory tract is common.

• #20 Respiratory Syncytial Virus (RSV) Pathophysiology

  https://pro.campus.sanofi/us/articles/rsv-physiopathology

  Respiratory syncytial virus (RSV) is a common and highly contagious virus that primarily affects the respiratory tract, particularly in infants and young children. RSV pathology is characterized by infection of respiratory epithelial cells, which triggers a variety of immune and inflammatory events. These early host immune responses to RSV are critical determinants of the progression of the disease and whether it develops into RSV bronchiolitis pathophysiology. […] Once spread via respiratory droplets, the RSV mechanism of infection begins with replication of the virus in the nasopharynx, where it rapidly spreads into the respiratory tract and targets apical ciliated epithelial cells. From there, the virus binds to cellular receptors, fuses with the host cell membrane, and inserts its nucleocapsid into the host cell to begin intracellular replication. Two important glycoproteins are involved in this RSV mechanism of action: the attachment glycoprotein (G) and the fusion glycoprotein (F), which mediate viral cell entry. Along with mediating cell entry, glycoprotein F triggers the merging of adjacent cells, giving rise to large multinucleated structures called syncytia, which cause epithelial lesions in the upper respiratory tract. Progression to the lower respiratory tract is common.

• #21

  https://historyofvaccines.org/diseases/respiratory-syncytial-virus/

  RSV is an RNA virus from the family of viruses in the genus. The virus has two subgroups: A and B. […] Like other viruses, RSV enters the cell and sheds its protein coat. Its RNA (genetic material) is then copied into a corresponding messenger RNA (mRNA) strand. The host cell machinery then takes up that mRNA to produce virus proteins that are then assembled into new virus particles. After enough virus particles are created, the cell develops surface projections and binds to other cells. These bound cells are known as syncytia, which gives the virus its name. […] The immune system reacts to syncytial cells by destroying them, or they are destroyed during viral replication. It is this destruction and immune response that cause symptoms. When the cells and tissues are damaged enough, the condition can be life-threatening.

• #22 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The downstream signals of EGFR lead to actin rearrangement, wrinkles on the plasma membrane and phagocytosis of liquid and RSV via macropinosomes upon extension of the plasma membrane. […] The RSV genome contains noncoding regions, namely, the leader region and tailer region, at the 3′ and 5′ ends, respectively. […] The polymerase continues to slide along the gene sequence after the GE signal until the next GS signal is activated to synthesize the next subgenomic mRNA. […] The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication.

• #23 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The downstream signals of EGFR lead to actin rearrangement, wrinkles on the plasma membrane and phagocytosis of liquid and RSV via macropinosomes upon extension of the plasma membrane. […] The RSV genome contains noncoding regions, namely, the leader region and tailer region, at the 3′ and 5′ ends, respectively. […] The polymerase continues to slide along the gene sequence after the GE signal until the next GS signal is activated to synthesize the next subgenomic mRNA. […] The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication.

• #24 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  The ultimate goals of these therapeutic measures are to alleviate symptoms, decrease the duration and severity of the illness, and decrease the risk of transmission. […] RSV infects and replicates in the mucosa lining the respiratory tract from the nasopharynx to the distal alveoli. […] Histological analyses of such patients have shown that most pathological changes in acute bronchiolitis involve the medium and small bronchioles (150 μm and smaller). In these infected bronchioles, airway obstruction is caused by airway edema, epithelial cell injury with the accumulation of inflammatory cells and other cellular debris, and increased airway mucus. […] This complex interplay between the viral genome and host immune system can result in a type-2 immune response and the release of pro-inflammatory cytokines that, in turn, activate mucus metaplasia and mucin secretion, further exaggerating airway obstruction.

• #25 Respiratory Syncytial Virus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971488-overview

  RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the lower respiratory tract and most often manifests as the clinical entity of bronchiolitis. Inoculation of the virus occurs in respiratory epithelial cells of the upper respiratory tract. Spread of the virus down the respiratory tract occurs through cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract. […] The illness may begin with upper respiratory symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever ( 101F), and decreased oral intake. […] The incidence of concomitant or secondary serious bacterial infection in association with RSV infection appears to be quite low ( 1%), with the exception of otitis media, which may occur in as many as 40% of cases.

• #26 Respiratory Syncytial Virus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971488-overview

  RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the lower respiratory tract and most often manifests as the clinical entity of bronchiolitis. Inoculation of the virus occurs in respiratory epithelial cells of the upper respiratory tract. Spread of the virus down the respiratory tract occurs through cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract. […] The illness may begin with upper respiratory symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever ( 101F), and decreased oral intake. […] The incidence of concomitant or secondary serious bacterial infection in association with RSV infection appears to be quite low ( 1%), with the exception of otitis media, which may occur in as many as 40% of cases.

• #27 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  The ultimate goals of these therapeutic measures are to alleviate symptoms, decrease the duration and severity of the illness, and decrease the risk of transmission. […] RSV infects and replicates in the mucosa lining the respiratory tract from the nasopharynx to the distal alveoli. […] Histological analyses of such patients have shown that most pathological changes in acute bronchiolitis involve the medium and small bronchioles (150 μm and smaller). In these infected bronchioles, airway obstruction is caused by airway edema, epithelial cell injury with the accumulation of inflammatory cells and other cellular debris, and increased airway mucus. […] This complex interplay between the viral genome and host immune system can result in a type-2 immune response and the release of pro-inflammatory cytokines that, in turn, activate mucus metaplasia and mucin secretion, further exaggerating airway obstruction.

• #28 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  The ultimate goals of these therapeutic measures are to alleviate symptoms, decrease the duration and severity of the illness, and decrease the risk of transmission. […] RSV infects and replicates in the mucosa lining the respiratory tract from the nasopharynx to the distal alveoli. […] Histological analyses of such patients have shown that most pathological changes in acute bronchiolitis involve the medium and small bronchioles (150 μm and smaller). In these infected bronchioles, airway obstruction is caused by airway edema, epithelial cell injury with the accumulation of inflammatory cells and other cellular debris, and increased airway mucus. […] This complex interplay between the viral genome and host immune system can result in a type-2 immune response and the release of pro-inflammatory cytokines that, in turn, activate mucus metaplasia and mucin secretion, further exaggerating airway obstruction.

• #29 Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV)

  https://www.mdpi.com/2076-0817/12/2/154

  The ultimate goals of these therapeutic measures are to alleviate symptoms, decrease the duration and severity of the illness, and decrease the risk of transmission. […] RSV infects and replicates in the mucosa lining the respiratory tract from the nasopharynx to the distal alveoli. […] Histological analyses of such patients have shown that most pathological changes in acute bronchiolitis involve the medium and small bronchioles (150 μm and smaller). In these infected bronchioles, airway obstruction is caused by airway edema, epithelial cell injury with the accumulation of inflammatory cells and other cellular debris, and increased airway mucus. […] This complex interplay between the viral genome and host immune system can result in a type-2 immune response and the release of pro-inflammatory cytokines that, in turn, activate mucus metaplasia and mucin secretion, further exaggerating airway obstruction.

• #30 Respiratory Syncytial Virus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971488-overview

  RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the lower respiratory tract and most often manifests as the clinical entity of bronchiolitis. Inoculation of the virus occurs in respiratory epithelial cells of the upper respiratory tract. Spread of the virus down the respiratory tract occurs through cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract. […] The illness may begin with upper respiratory symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever ( 101F), and decreased oral intake. […] The incidence of concomitant or secondary serious bacterial infection in association with RSV infection appears to be quite low ( 1%), with the exception of otitis media, which may occur in as many as 40% of cases.

• #31 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  RSV preferentially infects the apical, but not basolateral, surface of the airway epithelial cells. […] RSV seems to specifically target luminal columnar cells after they have developed cilia. […] RSV is also shed from the apical surface, and the beating of the cilia may facilitate spreading of the infection to neighboring ciliated cells. […] RSV expresses two nonstructural (NS) proteins, NS1 and NS2, which reduce the induction of the type I IFNs, IFN-1, IFN-2, and IFN-3. […] These results suggest there is a link between the NS1 and NS2 inhibition of the host cytokine response and the ability to control viral replication. […] Autopsy studies of children who die of RSV bronchiolitis reveal that the inflammation generated by the immune response may be an important pathogenic factor, and that airway obstruction is an important component of the disease.

• #32 Respiratory Syncytial Virus (RSV): Replication, Pathogenesis • Microbe Online

  https://microbeonline.com/respiratory-syncytial-virus-rsv-replication-pathogenesis/

  RSV replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. […] There is lymphocyte migration, resulting in peribronchiolar infiltration; submucosal tissues become edematous; and plugs consisting of mucus, cellular debris, and fibrin occlude the smaller bronchioles. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells in the plugs but are seldom detected in the small bronchioles. […] Viremia occurs rarely if at all. […] An intact immune system seems to be important in resolving an infection, as patients with impaired cell-mediated immunity may become persistently infected with a respiratory syncytial virus and shed the virus for months.

• #33 Respiratory Syncytial Virus (RSV): Replication, Pathogenesis • Microbe Online

  https://microbeonline.com/respiratory-syncytial-virus-rsv-replication-pathogenesis/

  RSV replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. […] There is lymphocyte migration, resulting in peribronchiolar infiltration; submucosal tissues become edematous; and plugs consisting of mucus, cellular debris, and fibrin occlude the smaller bronchioles. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells in the plugs but are seldom detected in the small bronchioles. […] Viremia occurs rarely if at all. […] An intact immune system seems to be important in resolving an infection, as patients with impaired cell-mediated immunity may become persistently infected with a respiratory syncytial virus and shed the virus for months.

• #34 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] The main cell to be infected by RSV is the respiratory epithelial cell (AEC). […] In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway.

• #35 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #36 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #37 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #38 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #39 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #40 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  RSV preferentially infects the apical, but not basolateral, surface of the airway epithelial cells. […] RSV seems to specifically target luminal columnar cells after they have developed cilia. […] RSV is also shed from the apical surface, and the beating of the cilia may facilitate spreading of the infection to neighboring ciliated cells. […] RSV expresses two nonstructural (NS) proteins, NS1 and NS2, which reduce the induction of the type I IFNs, IFN-1, IFN-2, and IFN-3. […] These results suggest there is a link between the NS1 and NS2 inhibition of the host cytokine response and the ability to control viral replication. […] Autopsy studies of children who die of RSV bronchiolitis reveal that the inflammation generated by the immune response may be an important pathogenic factor, and that airway obstruction is an important component of the disease.

• #41 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  RSV preferentially infects the apical, but not basolateral, surface of the airway epithelial cells. […] RSV seems to specifically target luminal columnar cells after they have developed cilia. […] RSV is also shed from the apical surface, and the beating of the cilia may facilitate spreading of the infection to neighboring ciliated cells. […] RSV expresses two nonstructural (NS) proteins, NS1 and NS2, which reduce the induction of the type I IFNs, IFN-1, IFN-2, and IFN-3. […] These results suggest there is a link between the NS1 and NS2 inhibition of the host cytokine response and the ability to control viral replication. […] Autopsy studies of children who die of RSV bronchiolitis reveal that the inflammation generated by the immune response may be an important pathogenic factor, and that airway obstruction is an important component of the disease.

• #42 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #43 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #44 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway. […] The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A recent study showed that neutrophils could significantly regulate RSV latent infection and reduce the exacerbation of asthma in children through phagocytosis facilitated by the carcinoembryonic antigen-associated cell adhesion molecule 3 (CEACAM3) protein. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI).

• #45 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #46 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway. […] The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A recent study showed that neutrophils could significantly regulate RSV latent infection and reduce the exacerbation of asthma in children through phagocytosis facilitated by the carcinoembryonic antigen-associated cell adhesion molecule 3 (CEACAM3) protein. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI).

• #47 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #48 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] Then, we discuss the latest findings related to the pathogenesis of RSV. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #49 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  The primary target of RSV infection in the mouse model is the type 1 alveolar pneumocyte, and illness is a consequence of infection at this level of the lung. […] RSV has been reported to inhibit alveolar fluid clearance, a crucial function of bronchoalveolar epithelium. […] RSV infection also led to an increase in concentration of uridine triphosphate in bronchoalveolar lavage fluid from an unidentified source. […] RSV infection in the setting of allergic inflammation or the absence of STAT1-mediated signaling induces airway epithelial mucus that is associated with the expression of IL-17, a cytokine recently described to regulate mucus production. […] RSV-induced cytokines and chemokines have direct effector functions that impact disease, and are important for the recruitment and differentiation of the T-lymphocyte response. […] Further exploration of the factors that regulate RSV pathogenesis, including investigation beyond the classical Th1/Th2 paradigm, will be critical for developing effective therapies and safe vaccines against this important pathogen.

• #50 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway. […] The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A recent study showed that neutrophils could significantly regulate RSV latent infection and reduce the exacerbation of asthma in children through phagocytosis facilitated by the carcinoembryonic antigen-associated cell adhesion molecule 3 (CEACAM3) protein. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI).

• #51 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway. […] The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A recent study showed that neutrophils could significantly regulate RSV latent infection and reduce the exacerbation of asthma in children through phagocytosis facilitated by the carcinoembryonic antigen-associated cell adhesion molecule 3 (CEACAM3) protein. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI).

• #52 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #53 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. […] In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. […] Then, we discuss the latest findings related to the pathogenesis of RSV. […] The immune response in patients infected with RSV causes neutrophils to infiltrate and narrow the airways, leading to respiratory diseases such as bronchiolitis. […] RSV infection can induce microtubule-/dynein-dependent mitochondria to gather around the nucleus and translocate to the center of the microtubule tissue.

• #54 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] The main cell to be infected by RSV is the respiratory epithelial cell (AEC). […] In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway.

• #55 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #56 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20211120/Infant-respiratory-syncytial-virus-infection-results-in-metabolic-reprogramming-of-airway-epithelial-cells.aspx

  Infection with respiratory syncytial virus during infancy results in metabolic reprogramming of epithelial cells lining the airway, according to a Northwestern Medicine study published in the journal Viruses. […] This mechanism may explain why childhood infections from respiratory syncytial virus (RSV) are associated with dramatically higher rates of asthma and other wheezing illnesses, said Sergejs Berdnikovs, PhD, associate professor of Medicine in the Division of Allergy and Immunology and co-senior author of the study. […] The scientists discovered that epithelial cells from children infected with RSV in the first year of life consumed much more glucose compared to normal cells. […] These metabolically „hyperactive” epithelial cells may lead to the development of childhood asthma, by disrupting the natural function of the airway epithelium as a barrier that separates and protects the body from substances in the air. […] Berdnikovs and Hartert said they are now planning a cohort study, where they will follow children from birth to measure metabolic changes in the airway epithelium before and after RSV infection, helping firmly determine the temporal cause-and-effect relationship.

• #57 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20211120/Infant-respiratory-syncytial-virus-infection-results-in-metabolic-reprogramming-of-airway-epithelial-cells.aspx

  Infection with respiratory syncytial virus during infancy results in metabolic reprogramming of epithelial cells lining the airway, according to a Northwestern Medicine study published in the journal Viruses. […] This mechanism may explain why childhood infections from respiratory syncytial virus (RSV) are associated with dramatically higher rates of asthma and other wheezing illnesses, said Sergejs Berdnikovs, PhD, associate professor of Medicine in the Division of Allergy and Immunology and co-senior author of the study. […] The scientists discovered that epithelial cells from children infected with RSV in the first year of life consumed much more glucose compared to normal cells. […] These metabolically „hyperactive” epithelial cells may lead to the development of childhood asthma, by disrupting the natural function of the airway epithelium as a barrier that separates and protects the body from substances in the air. […] Berdnikovs and Hartert said they are now planning a cohort study, where they will follow children from birth to measure metabolic changes in the airway epithelium before and after RSV infection, helping firmly determine the temporal cause-and-effect relationship.

• #58 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] The main cell to be infected by RSV is the respiratory epithelial cell (AEC). […] In infected cells, the transcription of viral genes should encode NS1 and NS2 proteins initially, which are essential for host infection, and their function is to inhibit the type interferon (IFN-) response and other components of the immune system. […] A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway.

• #59 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  These changes lead to impairment of mitochondrial respiratory function, loss of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS), which in turn increase the replication and titer of RSV. […] RSV infection is most likely to affect the respiratory system, with most of the damage to the airway mediated by the immune response, not by the virus replication itself. […] In AEC, RSV F inhibits the production of interferon- (IFN-) induced by interferon regulatory factor (IRF) 1 (the most critical type III IFN in the antiviral immune response to RSV infection) by inducing EGFR activation, which leads to a continuous increase in viral infection. […] The NS1 and NS2 complexes are transported to mitochondria to form degradosome, which can degrade a variety of proteins in the IFN- pathway.

• #60 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #61 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #62 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #63 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #64 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #65 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #66 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #67 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #68 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  Genetic variations in viral epitopes and adjacent regions affect protein folding, post-transcriptional modifications, and antigenic processing, influencing B and T cell immunity during viral infections. This alteration in conformation can lead to immune evasion, potentially impacting disease severity, outbreaks, and reinfections. Notably, the variability observed in the G gene, followed by the SH and F genes, suggests a correlation between structural differences in proteins and their immunogenicity. Specifically, the irregular curl and low bond energy of the G protein make it prone to conformational changes, affecting its immunogenicity and potentially modulating the immune response. […] Different genotypes of RSV exhibit variations in the structural conformation of key proteins such as G, SH, and F, impacting immune responses. The emergence of novel genotypes like ON1 and BA9 is associated with distinct structural differences, particularly in the G protein, which may contribute to immune evasion. Evidence suggests that RSV glycoprotein G plays a crucial role in immune modulation during infection, affecting cytokine expression and the antiviral response.

• #69 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #70 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #71 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The downstream signals of EGFR lead to actin rearrangement, wrinkles on the plasma membrane and phagocytosis of liquid and RSV via macropinosomes upon extension of the plasma membrane. […] The RSV genome contains noncoding regions, namely, the leader region and tailer region, at the 3′ and 5′ ends, respectively. […] The polymerase continues to slide along the gene sequence after the GE signal until the next GS signal is activated to synthesize the next subgenomic mRNA. […] The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication.

• #72 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #73 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #74 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #75 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #76

  https://www.jci.org/articles/view/185689

  Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. […] Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. […] Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. […] Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium.

• #77

  https://www.jci.org/articles/view/185689

  Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. […] Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. […] Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. […] Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium.

• #78

  https://www.jci.org/articles/view/185689

  Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. […] Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. […] Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. […] Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium.

• #79

  https://www.jci.org/articles/view/185689

  Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. […] Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. […] Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. […] Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium.

• #80

  https://www.jci.org/articles/view/185689

  Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. […] Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. […] Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. […] Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium.

• #81

  https://www.jci.org/articles/view/185689

  Zhao et al. importantly illustrate cell-autonomous STAT3 hyporesponsiveness of pediatric respiratory epithelial cells that increases apoptosis and shedding of RSV-infected cells, thus facilitating virus spread. […] Countering viral susceptibility by enhancing STAT3 activity or downstream effector pathways is not without risk, as STAT3 gain of function mutations trigger autoimmunity. […] Whether the STAT3 pathway can be safely exploited for effective antiviral therapy remains a future challenge.

• #82

  https://www.jci.org/articles/view/185689

  Zhao et al. importantly illustrate cell-autonomous STAT3 hyporesponsiveness of pediatric respiratory epithelial cells that increases apoptosis and shedding of RSV-infected cells, thus facilitating virus spread. […] Countering viral susceptibility by enhancing STAT3 activity or downstream effector pathways is not without risk, as STAT3 gain of function mutations trigger autoimmunity. […] Whether the STAT3 pathway can be safely exploited for effective antiviral therapy remains a future challenge.

• #83

  https://www.jci.org/articles/view/185689

  Zhao et al. importantly illustrate cell-autonomous STAT3 hyporesponsiveness of pediatric respiratory epithelial cells that increases apoptosis and shedding of RSV-infected cells, thus facilitating virus spread. […] Countering viral susceptibility by enhancing STAT3 activity or downstream effector pathways is not without risk, as STAT3 gain of function mutations trigger autoimmunity. […] Whether the STAT3 pathway can be safely exploited for effective antiviral therapy remains a future challenge.

• #84 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8495404/

  The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI). […] The RSV F protein is anchored on the surface of the RSV membrane by a transmembrane domain and is a 'spring-loaded’ trimer. […] RSV infection activates ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1) in an RSV G protein-dependent manner, which in turn causes tyrosine kinase c-Src to transactivate EGFR through phosphorylation at EGFR Tyr845.

• #85 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A variety of cell-derived (such as alveolar macrophages and dendric cells) IL-33 can be triggered in the process of RSV infection, which is thought to depend on the activation of MAPK signaling pathway. […] The accumulation of these inflammatory factors further recruits a large number of granulocytes (such as neutrophils) to the infected site. […] A recent study showed that neutrophils could significantly regulate RSV latent infection and reduce the exacerbation of asthma in children through phagocytosis facilitated by the carcinoembryonic antigen-associated cell adhesion molecule 3 (CEACAM3) protein. […] The expression of some bacterial receptors, such as intercellular adhesion molecule-1 (ICAM-1), platelet activating factor-receptor (PAF-r) and carcinoembryonic antigen-associated cellular adhesion molecule 1 (CEACAM1), was induced during RSV infection, which enhances the binding of bacteria to prolong lower respiratory tract infection (LRTI).

• #86 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #87 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #88 Sequence Studies of Respiratory Syncytial Virus (RSV) From a 2012-2013 Community Outbreak in USA to Identify Signature Sequences Associated With Disease Severity and Transmission | J. Craig Venter Institute

  https://www.jcvi.org/research/sequence-studies-respiratory-syncytial-virus-rsv-2012-2013-community-outbreak-usa-identify

  We will also measure cytokine/chemokine levels in nasal washes to define how RSV strains impact bronchiolitis, inflammation, and wheezing. […] RSV genotypes and/or mutations associated with clinical disease will be studied functionally. […] The mouse model of RSV pathogenesis that we have developed utilizes quantitative, digital pathology, pulmonary pathophysiology, and recapitulates RSV-induced mucus expression. […] It will also provide the detailed sequence data needed to identify strains with common lineage and understand change during the course of the outbreak and identify changes that may have selective advantage to the virus. […] Infants at risk for RSV infection and subsequent asthma have been frequently found to have bacterial super-infections and there are high incidences of pulmonary bacterial coinfection in children with severe respiratory syncytial virus (RSV) bronchiolitis.

• #89 Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

  https://www.ijbs.com/v17p4073.htm

  A growing body of evidence suggests that severe RSV disease is associated with an inadequate immune response and a low viral load. […] RSV inhibited the humoral immune response of B cells by negatively regulating the expression of IL-21R on the surface of T follicular helper (TFH) cells and IL-21 in immature B cells. […] The severity of bronchiolitis and wheezing disease was related to other factors, such as respiratory bacteria. […] These results suggest that airways damaged by RSV infection may be more vulnerable to secondary bacterial infection. […] The development of small-molecule inhibitors of RSV infection is mainly based on two modes of action: in one mode, the invading virions are blocked from binding to the F protein on the surface of RSV, and in the other mode, the production of new virions is inhibited by blocking viral transcription and replication. […] The N protein, which is an important component of the polymerase complex and the most conserved viral protein that plays an indispensable role in RNA transcription and replication, is a potentially interesting target.

• #90 Respiratory Syncytial Virus Infection: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/971488-overview

  RSV infection is limited to the respiratory tract. Initial infection in young infants or children frequently involves the lower respiratory tract and most often manifests as the clinical entity of bronchiolitis. Inoculation of the virus occurs in respiratory epithelial cells of the upper respiratory tract. Spread of the virus down the respiratory tract occurs through cell-to-cell transfer of the virus along intracytoplasmic bridges (syncytia) from the upper to the lower respiratory tract. […] The illness may begin with upper respiratory symptoms and progress rapidly over 1-2 days to the development of diffuse small airway disease characterized by cough, coryza, wheezing and rales, low-grade fever ( 101F), and decreased oral intake. […] The incidence of concomitant or secondary serious bacterial infection in association with RSV infection appears to be quite low ( 1%), with the exception of otitis media, which may occur in as many as 40% of cases.

• #91 Sequence Studies of Respiratory Syncytial Virus (RSV) From a 2012-2013 Community Outbreak in USA to Identify Signature Sequences Associated With Disease Severity and Transmission | J. Craig Venter Institute

  https://www.jcvi.org/research/sequence-studies-respiratory-syncytial-virus-rsv-2012-2013-community-outbreak-usa-identify

  As the single most important cause of serious lower respiratory tract disease in infants and young children in the United States and globally, RSV is of considerable public health importance and a high priority for vaccine development. […] RSV causes lower respiratory tract illness and potentiates childhood wheezing and asthma. […] It has been found that RSV pathogenicity is strain-dependent in the mouse model. […] To establish that specific RSV genotypes of virulent RSV strains are associated with early childhood wheezing, severe acute bronchiolitis and subsequent asthma development and asthma pathogenesis, plan to utilize RSV isolates obtained from a retrospective bronchiolitis-to-asthma infant cohort (INSPIRE) with defined parameters of illness such as bronchiolitis severity score (BSS) and prolonged wheezing.

• #92 Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-8-43

  Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs). […] The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

• #93

  https://link.springer.com/article/10.1007/s11882-012-0278-z

  A similar study examined a variety of RSV strains (A2 and 3 clinical isolates: BT2a, BT3a, BT4a) in primary human bronchial epithelial cells (PBECs) from healthy children. […] Recent advancements in RSV research have illuminated the signal transduction pathways that are activated to initiate transcription of inflammatory cytokines and chemokines once RSV is recognized by a TLR on the cell surface.

• #94 Respiratory Syncytial Virus Infection in Children | AAFP

  https://www.aafp.org/pubs/afp/issues/2011/0115/p141.html

  Respiratory syncytial virus (RSV) is an RNA virus that causes respiratory tract infections in children. Bronchiolitis, a lower respiratory tract infection, is often caused by RSV. An RSV infection begins with replication of the virus in the nasopharynx. The virus spreads to the small bronchiolar epithelium lining the small airways within the lungs, and a lower respiratory tract infection can begin in one to three days. If a lower respiratory tract infection occurs, it causes edema, increased mucus production, and eventual necrosis and regeneration of these epithelial cells. This leads to small airway obstruction, air trapping, and increased airway resistance. […] RSV is an enveloped, nonsegmented, negative-stranded RNA virus and a member of the Paramyxoviridae family. Two subtypes, A and B, are present in most outbreaks. Subtype A usually causes more severe disease. The dominant strains shift each year, which may account for frequent reinfections. The incubation period ranges from two to eight days; viral shedding ranges from three to eight days, although it may continue for up to four weeks in young infants.

• #95 Sequence Studies of Respiratory Syncytial Virus (RSV) From a 2012-2013 Community Outbreak in USA to Identify Signature Sequences Associated With Disease Severity and Transmission | J. Craig Venter Institute

  https://www.jcvi.org/research/sequence-studies-respiratory-syncytial-virus-rsv-2012-2013-community-outbreak-usa-identify

  As the single most important cause of serious lower respiratory tract disease in infants and young children in the United States and globally, RSV is of considerable public health importance and a high priority for vaccine development. […] RSV causes lower respiratory tract illness and potentiates childhood wheezing and asthma. […] It has been found that RSV pathogenicity is strain-dependent in the mouse model. […] To establish that specific RSV genotypes of virulent RSV strains are associated with early childhood wheezing, severe acute bronchiolitis and subsequent asthma development and asthma pathogenesis, plan to utilize RSV isolates obtained from a retrospective bronchiolitis-to-asthma infant cohort (INSPIRE) with defined parameters of illness such as bronchiolitis severity score (BSS) and prolonged wheezing.

• #96 Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-8-43

  Our work sought to address whether the prototypic RSV strain A2 was representative of recent RSV clinical isolates in terms of cytopathogenesis, infectivity, virus growth kinetics, and pro-inflammatory immune responses. […] The mechanisms responsible for this differential cytopathogenicity remain to be elucidated and are the subject of ongoing research. […] Consequently, our findings suggest that the choice of RSV strain may have important implications for future studies on RSV pathogenesis and our understanding of the molecular mechanisms thereof.

• #97 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  There is substantial epidemiological evidence supporting the concept that respiratory syncytial virus (RSV) lower respiratory tract infection in infancy may be linked to the development of reactive airway disease (RAD) in childhood. […] However, much less is known concerning the mechanisms by which this self-limiting infection leads to airway dysfunction that persists long after the virus is cleared from the lungs. […] The pathogenetic mechanisms of RSV-induced airway inflammation and hyperreactivity remain largely unknown, however, and no effective therapeutic option is currently available to manage the acute and chronic clinical manifestations of this infection. […] Various theories have been put forth in an attempt to explain how RSV generates long-term airway inflammation and hyperreactivity.

• #98 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  There is substantial epidemiological evidence supporting the concept that respiratory syncytial virus (RSV) lower respiratory tract infection in infancy may be linked to the development of reactive airway disease (RAD) in childhood. […] However, much less is known concerning the mechanisms by which this self-limiting infection leads to airway dysfunction that persists long after the virus is cleared from the lungs. […] The pathogenetic mechanisms of RSV-induced airway inflammation and hyperreactivity remain largely unknown, however, and no effective therapeutic option is currently available to manage the acute and chronic clinical manifestations of this infection. […] Various theories have been put forth in an attempt to explain how RSV generates long-term airway inflammation and hyperreactivity.

• #99 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #100 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #101 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #102 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #103 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #104 Pathophysiological mechanisms for the respiratory syncytial virus-reactive airway disease link | Respiratory Research | Full Text

  https://respiratory-research.biomedcentral.com/articles/10.1186/rr185

  We have proposed that interactions between neural and immunoinflammatory mechanisms may cause inflammation well after the initial RSV infection is cleared. […] RSV upregulates the expression of the gene that encodes the NK1 receptor subtype, which mediates the inflammatory and immunomodulatory effects of substance P, thereby potentiating neurogenically mediated airway inflammation. […] RSV infection interferes with this physiologic decline, promoting a large increase in the expression of both NGF and neurotrophin receptors. […] RSV-induced release of NGF may lead to short-term and long-term changes in the distribution and reactivity of sensory nerves across the respiratory tract, contributing toward exaggerated inflammatory reactions during and after the infection. […] Based on this model, activation of the upregulated NANCe system by irritants would be responsible for the recurring airway inflammation and subsequent narrowing, which continues after the acute RSV infection has cleared. […] Preventing RSV is therefore a promising approach to reducing the incidence of RAD in childhood.

• #105 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  The primary target of RSV infection in the mouse model is the type 1 alveolar pneumocyte, and illness is a consequence of infection at this level of the lung. […] RSV has been reported to inhibit alveolar fluid clearance, a crucial function of bronchoalveolar epithelium. […] RSV infection also led to an increase in concentration of uridine triphosphate in bronchoalveolar lavage fluid from an unidentified source. […] RSV infection in the setting of allergic inflammation or the absence of STAT1-mediated signaling induces airway epithelial mucus that is associated with the expression of IL-17, a cytokine recently described to regulate mucus production. […] RSV-induced cytokines and chemokines have direct effector functions that impact disease, and are important for the recruitment and differentiation of the T-lymphocyte response. […] Further exploration of the factors that regulate RSV pathogenesis, including investigation beyond the classical Th1/Th2 paradigm, will be critical for developing effective therapies and safe vaccines against this important pathogen.

• #106 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  RSV primarily infects human epithelial cells within the nasopharynx; however, it can also infect other types of cells, including cell lines, but with much lower efficacy. Infection may lead to the formation of syncytia within the infected cell. Primary infection with RSV is generally exhibited as lower respiratory tract disease, pneumonia, bronchiolitis, tracheobronchitis, or upper respiratory tract illness. In infants, RSV infection causes approximately 70% of viral bronchiolitis cases. Common clinical symptoms include rhinorrhea, sneezing, coughing, pharyngitis, bronchitis, headache, fatigue, chest tightness, wheezing, dyspnea, and fever. In some cases, otitis media may occur. RSV infections usually begin with upper respiratory tract disease, which has the tendency to progress to lower respiratory tract disease (in ~50% cases). Symptoms begin 3-7 days post infection with RSV. Healthy individuals typically recover in 1-2 weeks, but it can take much longer if serious disease develops. RSV can cause long term-effects. Approximately half of the infants experience recurrent wheezing following RSV lower respiratory tract infection. Wheezing symptoms can persist for up to 5 years followed by a gradual decrease.

• #107 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  RSV has an RNA genome, thus its replication is RNA-dependent and it lacks proofreading mechanisms. This leads to many single nucleotide polymorphism (SNP) errors and other mutations. The constant change in the genome allows for changes in virulence and makes it difficult to develop vaccines and antiviral agents.

• #108 Respiratory syncytial virus: Infectious substances pathogen safety data sheet – Canada.ca

  https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/respiratory-syncytial-virus.html

  RSV has an RNA genome, thus its replication is RNA-dependent and it lacks proofreading mechanisms. This leads to many single nucleotide polymorphism (SNP) errors and other mutations. The constant change in the genome allows for changes in virulence and makes it difficult to develop vaccines and antiviral agents.

• #109 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #110 Respiratory syncytial virus – Wikipedia

  https://en.wikipedia.org/wiki/Respiratory_syncytial_virus

  The F protein is a major target for neutralizing antibodies, but its variability enables viral evasion from neutralization, affecting the efficacy of antibodies like Palivizumab. Cross-reactions between RSV subtypes and genotypes are observed, but immune responses are subtype- or genotype-specific, indicating the impact of gene mutations, particularly in the G protein, on immune evasion. Additionally, differences in cytokine expression and immune cell responses highlight the complexity of immune interactions during RSV infection. Genomic variations in RSV, particularly in proteins like G and F, influence immune responses and contribute to immune evasion. This multifaceted immunomodulatory arsenal likely contributes to RSV’s ability to cause mild respiratory symptoms in most cases, yet it poses a severe threat to vulnerable populations such as infants and the elderly, potentially leading to life-threatening lung disease characterized by immune dysregulation. RSV has evolved numerous strategies to evade the host’s antiviral response, with over half of its proteins exerting immunomodulatory effects.

• #111 Respiratory Syncytial Virus – Enanta Pharmaceuticals

  https://www.enanta.com/pipeline/respiratory-syncytial-virus/

  Respiratory syncytial virus (RSV) causes severe lung infections, including bronchiolitis and pneumonia. High risk populations include premature babies, young infants, and children. However, the virus is not limited to affecting only babies and children. Adults aged 65 and older and people with weakened immune systems (e.g. organ transplant, chemotherapy) are also at high risk. […] In terms of prevalence, globally there are an estimated 33 million cases of RSV annually in children younger than 5 years of age, with about 3 million hospitalized and more than 100,000 dying each year from complications associated with the infection. […] Currently, no safe and effective treatments exist for RSV infection. […] As an N-protein inhibitor, zelicapavir directly disrupts the virus’ ability to replicate, as compared to fusion inhibitors that work by preventing cells from becoming infected while allowing viral replication to continue.

• #112 Respiratory Syncytial Virus – Enanta Pharmaceuticals

  https://www.enanta.com/pipeline/respiratory-syncytial-virus/

  Targeting the N-protein also allows for an expanded treatment window in vitro as compared to fusion inhibitors. […] Another advantage of targeting the N-protein is that it is the most conserved gene in the viral genome, indicating it is not as flexible to change as the F-protein. […] This results in a much higher barrier to resistance for zelicapavir as compared to fusion inhibitors. […] Zelicapavir has demonstrated a very high barrier to resistance in vitro and in vivo. […] Antiviral treatment for RSV, including zelicapavir, has the greatest potential to show optimal efficacy in high-risk populations, as these patients have reduced RSV immunity or other comorbidities which manifest in a longer duration of viral shedding and greater disease severity, allowing a bigger window to realize the full potential of zelicapavir. […] We are also developing EDP-323, an oral direct-acting antiviral selectively targeting the RSV L-protein, which, like the N-protein, is essential for RSV replication.

• #113 Respiratory Syncytial Virus – Enanta Pharmaceuticals

  https://www.enanta.com/pipeline/respiratory-syncytial-virus/

  Targeting the N-protein also allows for an expanded treatment window in vitro as compared to fusion inhibitors. […] Another advantage of targeting the N-protein is that it is the most conserved gene in the viral genome, indicating it is not as flexible to change as the F-protein. […] This results in a much higher barrier to resistance for zelicapavir as compared to fusion inhibitors. […] Zelicapavir has demonstrated a very high barrier to resistance in vitro and in vivo. […] Antiviral treatment for RSV, including zelicapavir, has the greatest potential to show optimal efficacy in high-risk populations, as these patients have reduced RSV immunity or other comorbidities which manifest in a longer duration of viral shedding and greater disease severity, allowing a bigger window to realize the full potential of zelicapavir. […] We are also developing EDP-323, an oral direct-acting antiviral selectively targeting the RSV L-protein, which, like the N-protein, is essential for RSV replication.

• #114 Respiratory Syncytial Virus – Enanta Pharmaceuticals

  https://www.enanta.com/pipeline/respiratory-syncytial-virus/

  Targeting the N-protein also allows for an expanded treatment window in vitro as compared to fusion inhibitors. […] Another advantage of targeting the N-protein is that it is the most conserved gene in the viral genome, indicating it is not as flexible to change as the F-protein. […] This results in a much higher barrier to resistance for zelicapavir as compared to fusion inhibitors. […] Zelicapavir has demonstrated a very high barrier to resistance in vitro and in vivo. […] Antiviral treatment for RSV, including zelicapavir, has the greatest potential to show optimal efficacy in high-risk populations, as these patients have reduced RSV immunity or other comorbidities which manifest in a longer duration of viral shedding and greater disease severity, allowing a bigger window to realize the full potential of zelicapavir. […] We are also developing EDP-323, an oral direct-acting antiviral selectively targeting the RSV L-protein, which, like the N-protein, is essential for RSV replication.

• #115 Respiratory Syncytial Virus – Enanta Pharmaceuticals

  https://www.enanta.com/pipeline/respiratory-syncytial-virus/

  Respiratory syncytial virus (RSV) causes severe lung infections, including bronchiolitis and pneumonia. High risk populations include premature babies, young infants, and children. However, the virus is not limited to affecting only babies and children. Adults aged 65 and older and people with weakened immune systems (e.g. organ transplant, chemotherapy) are also at high risk. […] In terms of prevalence, globally there are an estimated 33 million cases of RSV annually in children younger than 5 years of age, with about 3 million hospitalized and more than 100,000 dying each year from complications associated with the infection. […] Currently, no safe and effective treatments exist for RSV infection. […] As an N-protein inhibitor, zelicapavir directly disrupts the virus’ ability to replicate, as compared to fusion inhibitors that work by preventing cells from becoming infected while allowing viral replication to continue.

• #116 Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713314/

  The primary target of RSV infection in the mouse model is the type 1 alveolar pneumocyte, and illness is a consequence of infection at this level of the lung. […] RSV has been reported to inhibit alveolar fluid clearance, a crucial function of bronchoalveolar epithelium. […] RSV infection also led to an increase in concentration of uridine triphosphate in bronchoalveolar lavage fluid from an unidentified source. […] RSV infection in the setting of allergic inflammation or the absence of STAT1-mediated signaling induces airway epithelial mucus that is associated with the expression of IL-17, a cytokine recently described to regulate mucus production. […] RSV-induced cytokines and chemokines have direct effector functions that impact disease, and are important for the recruitment and differentiation of the T-lymphocyte response. […] Further exploration of the factors that regulate RSV pathogenesis, including investigation beyond the classical Th1/Th2 paradigm, will be critical for developing effective therapies and safe vaccines against this important pathogen.

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