Materiały źródłowe

• #1 Pathogenesis of human cytomegalovirus in the immunocompromised host | Nature Reviews Microbiology

  https://www.nature.com/articles/s41579-021-00582-z

  Human cytomegalovirus (HCMV) is a herpesvirus that infects ~60% of adults in developed countries and more than 90% in developing countries. […] However, if the immune system is compromised, HCMV can replicate to high levels and cause serious end organ disease. […] Substantial progress is being made in understanding the natural history and pathogenesis of HCMV infection and disease in the immunocompromised host. […] In this Review, we discuss immune responses to HCMV and countermeasures deployed by the virus, the establishment of latency and reactivation from it, exogenous reinfection with additional strains, pathogenesis, development of end organ disease, indirect effects of infection, immune correlates of control of replication, current treatment strategies and the evaluation of novel vaccine candidates.

• #2 The pathogenesis of human cytomegalovirus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/25205255/

  Human cytomegalovirus (HCMV) is a recognized cause of disease in the fetus, the allograft recipient and AIDS patients. […] The epidemiology and molecular and cellular pathology of this virus are summarized to provide an overarching model of pathogenesis, able to account for these varying clinical presentations. […] In brief, HCMV has the potential to spread in the bloodstream to all organs, but only produces overt disease if the viral load increases to high levels. […] This is normally prevented by a robust immune response, so that the infected individual usually remains asymptomatic. […] However, this benefit comes at the cost of committing more and more immunological resources to controlling HCMV with time, so that the overall function of the immune system is impaired. […] Fortunately, recent progress in developing novel antiviral drugs and vaccines suggests the possibility that the diverse effects of HCMV may soon become controllable at the individual and population level, respectively.

• #3

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  These insights have opened new avenues for therapeutic intervention, including the development of novel antiviral compounds, vaccines, and immunotherapeutic approaches. […] HCMV possesses the largest genome among known human DNA viruses, spanning approximately 235250 kb and encoding over 170 proteins and featuring a complex virion structure consisting of a nucleocapsid, tegument layer, and glycoprotein-studded envelope. […] The HCMV life cycle is characterized by a temporal cascade of gene expression, categorized into immediate early (IE), early (E), and late (L) genes. […] HCMV can establish latency in certain cell types, particularly in CD34+ hematopoietic progenitor cells and CD14+ monocytes. […] During latency, viral gene expression is highly restricted, with only a subset of viral transcripts, including latency-associated transcripts, being expressed.

• #4 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  Cytomegalovirus (CMV) is a wide-spread virus, with manifestations ranging from asymptomatic to severe end-organ dysfunction in immunocompromised patients with congenital CMV disease. […] Human cytomegalovirus infections commonly are associated with the salivary glands. CMV infection may be asymptomatic in healthy people, but it can be life-threatening in an immunocompromised patient. […] After infection, CMV often remains latent, but it can reactivate at any time. Eventually, it causes mucoepidermoid carcinoma, and it may be responsible for prostate cancer. […] Of all herpes viruses, CMV harbors the largest number of genes dedicated to evading innate and adaptive immunity in the host. CMV represents a lifelong burden of antigenic T-cell surveillance and immune dysfunction. […] Once CMV is transmitted, and the primary infection clears, the virus remains dormant in myeloid cells. Vital replication and reactivation are contained primarily by cytotoxic T-cell immunity. However, when reactivation occurs, virions are released into the bloodstream and other body fluids, leading to the presence of symptoms, predominantly in immunocompromised patients.

• #5

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Reactivation from latency can occur under specific conditions, such as cellular differentiation or immune suppression, leading to productive infection and potential clinical manifestations. […] The molecular mechanisms of HCMV entry involve complex interactions between viral envelope glycoproteins and host cell receptors. […] The envelope glycoproteins embedded in the outermost virion envelope play major roles in binding to host cells, viral entry, and in some cases immune evasion. […] The gM/gN complex is considered the most abundant on the HCMV virion surface and initially interacts with cell surface heparan sulfate proteoglycans, potentially increasing HCMV virion concentration on the cell surface and promoting further interactions crucial for attachment during viral spread. […] gB is considered to be involved in membrane fusion and host cell entry, and it also interacts with heparan sulfate proteoglycans.

• #6

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Reactivation from latency can occur under specific conditions, such as cellular differentiation or immune suppression, leading to productive infection and potential clinical manifestations. […] The molecular mechanisms of HCMV entry involve complex interactions between viral envelope glycoproteins and host cell receptors. […] The envelope glycoproteins embedded in the outermost virion envelope play major roles in binding to host cells, viral entry, and in some cases immune evasion. […] The gM/gN complex is considered the most abundant on the HCMV virion surface and initially interacts with cell surface heparan sulfate proteoglycans, potentially increasing HCMV virion concentration on the cell surface and promoting further interactions crucial for attachment during viral spread. […] gB is considered to be involved in membrane fusion and host cell entry, and it also interacts with heparan sulfate proteoglycans.

• #7

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Reactivation from latency can occur under specific conditions, such as cellular differentiation or immune suppression, leading to productive infection and potential clinical manifestations. […] The molecular mechanisms of HCMV entry involve complex interactions between viral envelope glycoproteins and host cell receptors. […] The envelope glycoproteins embedded in the outermost virion envelope play major roles in binding to host cells, viral entry, and in some cases immune evasion. […] The gM/gN complex is considered the most abundant on the HCMV virion surface and initially interacts with cell surface heparan sulfate proteoglycans, potentially increasing HCMV virion concentration on the cell surface and promoting further interactions crucial for attachment during viral spread. […] gB is considered to be involved in membrane fusion and host cell entry, and it also interacts with heparan sulfate proteoglycans.

• #8

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

• #9

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Reactivation from latency can occur under specific conditions, such as cellular differentiation or immune suppression, leading to productive infection and potential clinical manifestations. […] The molecular mechanisms of HCMV entry involve complex interactions between viral envelope glycoproteins and host cell receptors. […] The envelope glycoproteins embedded in the outermost virion envelope play major roles in binding to host cells, viral entry, and in some cases immune evasion. […] The gM/gN complex is considered the most abundant on the HCMV virion surface and initially interacts with cell surface heparan sulfate proteoglycans, potentially increasing HCMV virion concentration on the cell surface and promoting further interactions crucial for attachment during viral spread. […] gB is considered to be involved in membrane fusion and host cell entry, and it also interacts with heparan sulfate proteoglycans.

• #10 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  CMV is a complex virus that appear to employ multiple strategies to evade the host immune system. […] When CMV enters the human body, it infects and penetrate virtually all types of cells, including monocytes, macrophages, neutrophils, neurons and hepatocytes. […] CMV also infect epithelial and endothelial cells it occurs through endocytosis. […] Primary CMV infection usually occurs during the first decades of life. […] Primary infection is followed by a latent infection that can persist throughout the life of the host. […] The primary infection results in the most severe disease especially when the host immunity is compromised. […] During latency, CMV cannot be eliminated by host defence but the immune system keeps the virus under close surveillance, giving it little chance to reactivate and cause symptomatic disease.

• #11 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Both replication of CMV DNA and morphogenesis of the virion capsid take place in the nucleus. Following maturation of the capsid, newly synthesized viral DNA is cleaved by an enzyme that results in packaging of linear genomic DNA. Subsequently, viral DNA-containing capsids acquire an inner layer of tegument proteins during their egress from the nucleus, including essential interactions between proteins and capsid protein, that stabilize the interaction between the capsid and the inner tegument layer of the virion. This then is transported along the cytoskeleton until the particle is enveloped. After this, the virus is released from the cell.

• #12 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Both replication of CMV DNA and morphogenesis of the virion capsid take place in the nucleus. Following maturation of the capsid, newly synthesized viral DNA is cleaved by an enzyme that results in packaging of linear genomic DNA. Subsequently, viral DNA-containing capsids acquire an inner layer of tegument proteins during their egress from the nucleus, including essential interactions between proteins and capsid protein, that stabilize the interaction between the capsid and the inner tegument layer of the virion. This then is transported along the cytoskeleton until the particle is enveloped. After this, the virus is released from the cell.

• #13

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  These insights have opened new avenues for therapeutic intervention, including the development of novel antiviral compounds, vaccines, and immunotherapeutic approaches. […] HCMV possesses the largest genome among known human DNA viruses, spanning approximately 235250 kb and encoding over 170 proteins and featuring a complex virion structure consisting of a nucleocapsid, tegument layer, and glycoprotein-studded envelope. […] The HCMV life cycle is characterized by a temporal cascade of gene expression, categorized into immediate early (IE), early (E), and late (L) genes. […] HCMV can establish latency in certain cell types, particularly in CD34+ hematopoietic progenitor cells and CD14+ monocytes. […] During latency, viral gene expression is highly restricted, with only a subset of viral transcripts, including latency-associated transcripts, being expressed.

• #14 Cytomegalovirus | PPT

  https://www.slideshare.net/slideshow/cytomegalovirus-36882501/36882501

  CMV – PATHOGENESIS WBCs and CD 13 + are reservoir cells Detected in most tissues of body and remains latent Enter host cell by fusion or phagocytosis Viral particles are made and assembled in nucleus, attain envelope by budding through inner nuclear membrane Replication produces immediate early (IE), early and late antigens IE (nucleus): direct production of viral and cellular genes Early (cytoplasm): directs viral DNA synthesis Late (Nucleus + Cytoplasm): directs production of structural nucleocapsid proteins Antivirals interrupt DNA synthesis […] CMV has the ability of lifelong persistent, latent infection, and can reactivate under certain conditions. In transplant recipients, infection with CMV from the donor organ or the reactivation of CMV in the recipient can lead to disease development.

• #15 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  The viral gene products that appear to play a role in chronic inflammation have evolved with CMVs and are likely unimportant for replication in vitro. […] The focus of the book is on the molecular and genomic aspects and the authors provide an insight into the current understanding of the subject and the future direction of research. […] The major immediate-early (MIE) regulatory region plays a key role in the control of lytic and latent infections. […] The MIE enhancer governs these outcomes by integrating a diverse array of input provided by the cell, the virus, and external surroundings. […] The degree of enhancer-dependent transcriptional activation determines the level of expression of the IE1 p72 and IE2 p86 proteins that are vital for viral replication. […] Human cytomegalovirus has evolved multiple mechanisms to manipulate the host cell’s metabolic and regulatory systems for the purposes of creating an environment favorable for productive infection.

• #16 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  The viral gene products that appear to play a role in chronic inflammation have evolved with CMVs and are likely unimportant for replication in vitro. […] The focus of the book is on the molecular and genomic aspects and the authors provide an insight into the current understanding of the subject and the future direction of research. […] The major immediate-early (MIE) regulatory region plays a key role in the control of lytic and latent infections. […] The MIE enhancer governs these outcomes by integrating a diverse array of input provided by the cell, the virus, and external surroundings. […] The degree of enhancer-dependent transcriptional activation determines the level of expression of the IE1 p72 and IE2 p86 proteins that are vital for viral replication. […] Human cytomegalovirus has evolved multiple mechanisms to manipulate the host cell’s metabolic and regulatory systems for the purposes of creating an environment favorable for productive infection.

• #17 Frontiers | Editorial: Cytomegalovirus Pathogenesis and Host Interactions

  https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.711551/full

  Human cytomegalovirus (HCMV) is a very widespread and highly prevalent β-herpesvirus, which sometimes causes mononucleosis following primary infection but is rarely associated with severe disease in immunocompetent individuals. […] However, like all herpesviruses, HCMV establishes infections that last for the life of the host in part by residing in a dormant state referred to as ‘latency’. […] Reactivation from latency or primary infection can cause debilitating damage in unborn children or life-threatening disease in immunosuppressed patients including recipients of solid organ or hematopoietic cell transplants. […] CMVs are highly sophisticated pathogens encoding hundreds of proteins and non-coding RNAs that engage in a myriad of host interactions. […] The study of these interactions is constantly revealing new and surprising insights into both the replication and persistence strategies of the virus as well as the biology of the host cell and organism.

• #18 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  Cytomegaloviruses are members of the herpesvirus group and can infect humans and other primates. […] The pathogenesis of infections with human cytomegalovirus (HCMV) have been modeled in small animals and primates utilizing the respective CMVs. In most cases, acute infection is associated with significant levels of virus replication and dissemination to multiple organs. […] The pathogenesis of acute HCMV infections can be readily explained by the control of virus replication and the resolution of virus-induced cytopathology. […] In contrast, chronic infections with CMV have as a major component of their pathogenesis a bi-directional relationship between viral gene expression and the host inflammatory response such that viral persistence is facilitated by the host inflammatory response and the host inflammatory response is fueled by the presence of the virus.

• #19 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  Cytomegaloviruses are members of the herpesvirus group and can infect humans and other primates. […] The pathogenesis of infections with human cytomegalovirus (HCMV) have been modeled in small animals and primates utilizing the respective CMVs. In most cases, acute infection is associated with significant levels of virus replication and dissemination to multiple organs. […] The pathogenesis of acute HCMV infections can be readily explained by the control of virus replication and the resolution of virus-induced cytopathology. […] In contrast, chronic infections with CMV have as a major component of their pathogenesis a bi-directional relationship between viral gene expression and the host inflammatory response such that viral persistence is facilitated by the host inflammatory response and the host inflammatory response is fueled by the presence of the virus.

• #20

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  These insights have opened new avenues for therapeutic intervention, including the development of novel antiviral compounds, vaccines, and immunotherapeutic approaches. […] HCMV possesses the largest genome among known human DNA viruses, spanning approximately 235250 kb and encoding over 170 proteins and featuring a complex virion structure consisting of a nucleocapsid, tegument layer, and glycoprotein-studded envelope. […] The HCMV life cycle is characterized by a temporal cascade of gene expression, categorized into immediate early (IE), early (E), and late (L) genes. […] HCMV can establish latency in certain cell types, particularly in CD34+ hematopoietic progenitor cells and CD14+ monocytes. […] During latency, viral gene expression is highly restricted, with only a subset of viral transcripts, including latency-associated transcripts, being expressed.

• #21

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  These insights have opened new avenues for therapeutic intervention, including the development of novel antiviral compounds, vaccines, and immunotherapeutic approaches. […] HCMV possesses the largest genome among known human DNA viruses, spanning approximately 235250 kb and encoding over 170 proteins and featuring a complex virion structure consisting of a nucleocapsid, tegument layer, and glycoprotein-studded envelope. […] The HCMV life cycle is characterized by a temporal cascade of gene expression, categorized into immediate early (IE), early (E), and late (L) genes. […] HCMV can establish latency in certain cell types, particularly in CD34+ hematopoietic progenitor cells and CD14+ monocytes. […] During latency, viral gene expression is highly restricted, with only a subset of viral transcripts, including latency-associated transcripts, being expressed.

• #22

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Reactivation from latency can occur under specific conditions, such as cellular differentiation or immune suppression, leading to productive infection and potential clinical manifestations. […] The molecular mechanisms of HCMV entry involve complex interactions between viral envelope glycoproteins and host cell receptors. […] The envelope glycoproteins embedded in the outermost virion envelope play major roles in binding to host cells, viral entry, and in some cases immune evasion. […] The gM/gN complex is considered the most abundant on the HCMV virion surface and initially interacts with cell surface heparan sulfate proteoglycans, potentially increasing HCMV virion concentration on the cell surface and promoting further interactions crucial for attachment during viral spread. […] gB is considered to be involved in membrane fusion and host cell entry, and it also interacts with heparan sulfate proteoglycans.

• #23 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  Reactivation of CMV infection from latency occurs in conditions, such as allograft rejection, sepsis, administration of Anti-leucocyte antibody (ALA) therapies. […] These clinical immune compromising conditions result in the release of cytokines and other pro-inflammatory mediators that play a role in the reactivation of virus from latency. […] Tumor necrosis factor (TNF)- is the primary cytokine responsible for reactivation of CMV from latency. […] TNF- binds to the TNF receptor on latently infected cells and activates protein kinase C and nuclear factor B (NF-B). […] In turn, NF-B acts on the immediate early promotor of the virus to activate virus replication. […] If the host cellular immune response is functioning properly, virus will be eliminated and host will recover. […] If the host T-cell response is impaired, virus multiplies causing inflammatory reactions. […] If the host is profoundly immune-compromised, virus multiplies exclusively causing tissue invasive disease and possibly death.

• #24 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  Reactivation of CMV infection from latency occurs in conditions, such as allograft rejection, sepsis, administration of Anti-leucocyte antibody (ALA) therapies. […] These clinical immune compromising conditions result in the release of cytokines and other pro-inflammatory mediators that play a role in the reactivation of virus from latency. […] Tumor necrosis factor (TNF)- is the primary cytokine responsible for reactivation of CMV from latency. […] TNF- binds to the TNF receptor on latently infected cells and activates protein kinase C and nuclear factor B (NF-B). […] In turn, NF-B acts on the immediate early promotor of the virus to activate virus replication. […] If the host cellular immune response is functioning properly, virus will be eliminated and host will recover. […] If the host T-cell response is impaired, virus multiplies causing inflammatory reactions. […] If the host is profoundly immune-compromised, virus multiplies exclusively causing tissue invasive disease and possibly death.

• #25

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

• #26 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  Cytomegalovirus (CMV) is a wide-spread virus, with manifestations ranging from asymptomatic to severe end-organ dysfunction in immunocompromised patients with congenital CMV disease. […] Human cytomegalovirus infections commonly are associated with the salivary glands. CMV infection may be asymptomatic in healthy people, but it can be life-threatening in an immunocompromised patient. […] After infection, CMV often remains latent, but it can reactivate at any time. Eventually, it causes mucoepidermoid carcinoma, and it may be responsible for prostate cancer. […] Of all herpes viruses, CMV harbors the largest number of genes dedicated to evading innate and adaptive immunity in the host. CMV represents a lifelong burden of antigenic T-cell surveillance and immune dysfunction. […] Once CMV is transmitted, and the primary infection clears, the virus remains dormant in myeloid cells. Vital replication and reactivation are contained primarily by cytotoxic T-cell immunity. However, when reactivation occurs, virions are released into the bloodstream and other body fluids, leading to the presence of symptoms, predominantly in immunocompromised patients.

• #27

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

• #28

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

• #29

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

• #30 Cytomegalovirus Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/cytomeg.htm

  CMV infections are usually subclinical. CMV is acquired from contaminated blood, tissue, and most body secretions. The virus infects epithelial cells, macrophages, and T lymphocytes. Epithelial cells when infected by CMV produce more virus. CMV is highly cell-associated and causes cells to coalesce to form large cells. The close cell interaction protects the virus from antibody inactivation. Cell-mediated immunity is required for resolution of symptoms and contributes to symptoms. CMV eventually becomes latent within T lymphocytes, endothelial cells, and macrophages. […] Suppression of cell-mediated immunity (e.g., HIV infection, corticosteroid use) allows recurrence of symptoms and can result in severe disease. The virus has the ability to induce immunosuppression during primary infections and reactivation of latent infections. CMV prevents expression of MHC I on the cell surface of an infected cell. It can also block cytokine-induced production of MHC-II on antigen presenting cells. This virus can also produce an IL-10 analogue that inhibits TH1 protective responses.

• #31 Cytomegalovirus Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/cytomeg.htm

  CMV infections are usually subclinical. CMV is acquired from contaminated blood, tissue, and most body secretions. The virus infects epithelial cells, macrophages, and T lymphocytes. Epithelial cells when infected by CMV produce more virus. CMV is highly cell-associated and causes cells to coalesce to form large cells. The close cell interaction protects the virus from antibody inactivation. Cell-mediated immunity is required for resolution of symptoms and contributes to symptoms. CMV eventually becomes latent within T lymphocytes, endothelial cells, and macrophages. […] Suppression of cell-mediated immunity (e.g., HIV infection, corticosteroid use) allows recurrence of symptoms and can result in severe disease. The virus has the ability to induce immunosuppression during primary infections and reactivation of latent infections. CMV prevents expression of MHC I on the cell surface of an infected cell. It can also block cytokine-induced production of MHC-II on antigen presenting cells. This virus can also produce an IL-10 analogue that inhibits TH1 protective responses.

• #32 Cytomegalovirus Infections

  https://www.atsu.edu/faculty/chamberlain/website/lectures/lecture/cytomeg.htm

  CMV infections are usually subclinical. CMV is acquired from contaminated blood, tissue, and most body secretions. The virus infects epithelial cells, macrophages, and T lymphocytes. Epithelial cells when infected by CMV produce more virus. CMV is highly cell-associated and causes cells to coalesce to form large cells. The close cell interaction protects the virus from antibody inactivation. Cell-mediated immunity is required for resolution of symptoms and contributes to symptoms. CMV eventually becomes latent within T lymphocytes, endothelial cells, and macrophages. […] Suppression of cell-mediated immunity (e.g., HIV infection, corticosteroid use) allows recurrence of symptoms and can result in severe disease. The virus has the ability to induce immunosuppression during primary infections and reactivation of latent infections. CMV prevents expression of MHC I on the cell surface of an infected cell. It can also block cytokine-induced production of MHC-II on antigen presenting cells. This virus can also produce an IL-10 analogue that inhibits TH1 protective responses.

• #33 Human cytomegalovirus – Wikipedia

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

  Lytically replicating viruses disrupt the cytoskeleton, causing massive cell enlargement, which is the source of the virus’ name. […] A study published in 2009 links infection with CMV to high blood pressure in mice, and suggests that the result of CMV infection of blood vessel endothelium in humans is a major cause of atherosclerosis. Researchers also found that when the cells were infected with CMV, they created renin, a protein known to contribute to high blood pressure. […] Human CMV causes cellular senescence, which could contribute to chronic inflammation (inflammaging). Human CMV is also linked to age-associated T cell dysfunction, contributing to immunosenescence. […] CMV encodes a protein, UL16, which is involved in the immune evasion of NK cell responses. It binds to ligands ULBP1, ULBP2 and MICB of NK cell activating receptor NKG2D, which prevents their surface expression. These ligands are normally upregulated in times of cellular stress, such as in viral infection, and by preventing their upregulation, CMV can prevent its host cell from dying due to NK cells.

• #34

  https://www.jci.org/articles/view/45449

  Following initial infection, a complex set of host responses conspires to limit CMV replication. […] Among the important recent advances has been the characterization of a previously unrecognized CMV entry pathway. […] Faced with such a breadth of host defense systems, the success of CMV in human infection has necessitated evolution of myriad viral evasion strategies. […] Millions of years of evolution have led CMV to establish an apparently benign relationship with its host, at least most of the time. […] However, CMV replication is poised in a delicate balance with host immune system controls, and even relatively minor perturbations, such as pregnancy or admission to an intensive care unit (ICU), allow CMV reactivation, often without overt CMV disease. […] The risk of acquiring CMV by transfusion from asymptomatic donors implicates blood as one site.

• #35 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #36 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #37 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #38 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #39 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #40

  https://step1.medbullets.com/microbiology/104109/cytomegalovirus-cmv

  CMV-caused diseases can either result from a primary infection or reactivation of a latent infection. […] Replication of host cells (including epithelial cells, macrophages, and neurons) result in viremia and symptoms from primary infection. […] Cellular immunity is crucial in clearing this virus.

• #41 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  Primary CMV infection is defined as infection in an individual who was previously CMV seronegative. In these patients, CMV immunoglobulin M (IgM) antibodies may be found as early as 4-7 weeks after initial infection and may persist as long as 16-20 weeks. Most neutralizing antibodies are directed against an envelope glycoprotein gB. Studies have shown that more than 50% of neutralizing activity in convalescent serum is attributable to glycoprotein gB. However, virion tegument proteins such as pp150, pp28, and pp65 evoke strong and durable antibody responses. […] CMV is an immunomodulatory virus and may aggravate underlying immune disorders (eg, SLE). […] Cell-mediated immunity is considered the most important factor in controlling CMV infection. Patients deficient in cell-mediated immunity are at greatest risk for CMV disease. CMV-specific CD4+ and CD8+ lymphocytes play an important role in immune protection after primary infection or reactivation of latent disease. Studies of bone marrow transplant recipients have revealed that those who do not develop CMV-specific CD4+ or CD8+ cells are at higher risk for CMV pneumonitis. Additionally, no cases of CMV pneumonia have been reported in allogeneic marrow transplant recipients receiving infusions of CMV-specific CD8+ cells.

• #42 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  CMV is a complex virus that appear to employ multiple strategies to evade the host immune system. […] When CMV enters the human body, it infects and penetrate virtually all types of cells, including monocytes, macrophages, neutrophils, neurons and hepatocytes. […] CMV also infect epithelial and endothelial cells it occurs through endocytosis. […] Primary CMV infection usually occurs during the first decades of life. […] Primary infection is followed by a latent infection that can persist throughout the life of the host. […] The primary infection results in the most severe disease especially when the host immunity is compromised. […] During latency, CMV cannot be eliminated by host defence but the immune system keeps the virus under close surveillance, giving it little chance to reactivate and cause symptomatic disease.

• #43 Human cytomegalovirus – Wikipedia

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

  Most healthy people who are infected by HCMV after birth have no symptoms. Some develop a syndrome similar to infectious mononucleosis or glandular fever, with prolonged fever, and a mild hepatitis. A sore throat is common. After infection, the virus remains latent in lymphocytes in the body for the rest of the person’s life. Overt disease rarely occurs unless immunity is suppressed either by drugs, infection or old age. Initial HCMV infection, which often is asymptomatic, is followed by a prolonged, inapparent infection during which the virus resides in mononuclear cells without causing detectable damage or clinical illness. […] Infectious CMV may be shed in the bodily fluids of any infected person, and can be found in urine, saliva, blood, tears, semen, and breast milk. The shedding of virus can occur intermittently, without any detectable signs or symptoms.

• #44

  https://step1.medbullets.com/microbiology/104109/cytomegalovirus-cmv

  CMV-caused diseases can either result from a primary infection or reactivation of a latent infection. […] Replication of host cells (including epithelial cells, macrophages, and neurons) result in viremia and symptoms from primary infection. […] Cellular immunity is crucial in clearing this virus.

• #45 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  CMV is a complex virus that appear to employ multiple strategies to evade the host immune system. […] When CMV enters the human body, it infects and penetrate virtually all types of cells, including monocytes, macrophages, neutrophils, neurons and hepatocytes. […] CMV also infect epithelial and endothelial cells it occurs through endocytosis. […] Primary CMV infection usually occurs during the first decades of life. […] Primary infection is followed by a latent infection that can persist throughout the life of the host. […] The primary infection results in the most severe disease especially when the host immunity is compromised. […] During latency, CMV cannot be eliminated by host defence but the immune system keeps the virus under close surveillance, giving it little chance to reactivate and cause symptomatic disease.

• #46 Frontiers | Editorial: Cytomegalovirus Pathogenesis and Host Interactions

  https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.711551/full

  Human cytomegalovirus (HCMV) is a very widespread and highly prevalent β-herpesvirus, which sometimes causes mononucleosis following primary infection but is rarely associated with severe disease in immunocompetent individuals. […] However, like all herpesviruses, HCMV establishes infections that last for the life of the host in part by residing in a dormant state referred to as ‘latency’. […] Reactivation from latency or primary infection can cause debilitating damage in unborn children or life-threatening disease in immunosuppressed patients including recipients of solid organ or hematopoietic cell transplants. […] CMVs are highly sophisticated pathogens encoding hundreds of proteins and non-coding RNAs that engage in a myriad of host interactions. […] The study of these interactions is constantly revealing new and surprising insights into both the replication and persistence strategies of the virus as well as the biology of the host cell and organism.

• #47 Cytomegalovirus (CMV) Infection – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection

  In patients who are immunocompromised, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. […] Antivirals may help treat retinitis but are less effective when other organs are affected. […] Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antivirals to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease.

• #48 Cytomegalovirus (CMV)-Replication, Transmission, Pathogenesis, Diseases, diagnosis and treatment – Online Biology Notes

  https://www.onlinebiologynotes.com/cytomegalovirus-cmv-replication-transmission-pathogenesis-diseases-diagnosis-and-treatment/

  CMV is a complex virus that appear to employ multiple strategies to evade the host immune system. […] When CMV enters the human body, it infects and penetrate virtually all types of cells, including monocytes, macrophages, neutrophils, neurons and hepatocytes. […] CMV also infect epithelial and endothelial cells it occurs through endocytosis. […] Primary CMV infection usually occurs during the first decades of life. […] Primary infection is followed by a latent infection that can persist throughout the life of the host. […] The primary infection results in the most severe disease especially when the host immunity is compromised. […] During latency, CMV cannot be eliminated by host defence but the immune system keeps the virus under close surveillance, giving it little chance to reactivate and cause symptomatic disease.

• #49 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  Cytomegaloviruses are members of the herpesvirus group and can infect humans and other primates. […] The pathogenesis of infections with human cytomegalovirus (HCMV) have been modeled in small animals and primates utilizing the respective CMVs. In most cases, acute infection is associated with significant levels of virus replication and dissemination to multiple organs. […] The pathogenesis of acute HCMV infections can be readily explained by the control of virus replication and the resolution of virus-induced cytopathology. […] In contrast, chronic infections with CMV have as a major component of their pathogenesis a bi-directional relationship between viral gene expression and the host inflammatory response such that viral persistence is facilitated by the host inflammatory response and the host inflammatory response is fueled by the presence of the virus.

• #50 Cytomegaloviruses: Molecular Biology and Immunology

  https://www.caister.com/cmv

  Cytomegaloviruses are members of the herpesvirus group and can infect humans and other primates. […] The pathogenesis of infections with human cytomegalovirus (HCMV) have been modeled in small animals and primates utilizing the respective CMVs. In most cases, acute infection is associated with significant levels of virus replication and dissemination to multiple organs. […] The pathogenesis of acute HCMV infections can be readily explained by the control of virus replication and the resolution of virus-induced cytopathology. […] In contrast, chronic infections with CMV have as a major component of their pathogenesis a bi-directional relationship between viral gene expression and the host inflammatory response such that viral persistence is facilitated by the host inflammatory response and the host inflammatory response is fueled by the presence of the virus.

• #51 Human Cytomegalovirus Infections and Mechanisms of Disease

  https://www.caister.com/hsp/abstracts/cmv/01.html

  The pathogenesis of infections with human cytomegalovirus (HCMV) have been modeled in small animals and primates utilizing the respective CMVs. In most cases, acute infection is associated with significant levels of virus replication and dissemination to multiple organs. […] The pathogenesis of acute HCMV infections can be readily explained by the control of virus replication and the resolution of virus-induced cytopathology. There appears to be a linkage between levels of virus replication, organ dysfunction, and disease in patients as well as in experimental models with acute CMV infections. […] In contrast, chronic infections with CMV have as a major component of their pathogenesis a bi-directional relationship between viral gene expression and the host inflammatory response such that viral persistence is facilitated by the host inflammatory response and the host inflammatory response is fueled by the presence of the virus. In these cases, disease can be attributed to both viral and host functions. The viral gene products that appear to play a role in chronic inflammation have evolved with CMVs and are likely unimportant for replication in vitro.

• #52 Cytomegalovirus | PPT

  https://www.slideshare.net/slideshow/cytomegalovirus-36882501/36882501

  CMV is still among the most important infectious complications after transplant. In the absence of prophylaxis, CMV reactivation can occur in over 75% of solid organ transplant recipients depending on other risk factors. Once CMV infection is established, then its replication is highly dynamic with rapid increases in viral load. CMV infection may lead to tissue invasive disease. […] CMV PATHOGENESIS Viral factors replication dynamics immune evasion viral heterogeneity viral co-infections Host factors CD4+, CD8+ T-cell NK cell, B-cell exogenous immunosuppression D/R immune status […] DIRECT EFFECTS OF CMV INFECTION CMV Viral Syndrome Fever, malaise, myalgias Leukopenia, thrombocytopenia, and other laboratory abnormalities Tissue Invasive Disease Hepatitis Pneumonitis Colitis Carditis Nephritis Pancreatitis Retinitis Direct Effects

• #53 Cytomegalovirus | PPT

  https://www.slideshare.net/slideshow/cytomegalovirus-36882501/36882501

  INDIRECT EFFECTS OF CMV INFECTION Altered host immune response Graft rejection; graft dysfunction Opportunistic infections: Bacterial fungal superinfection Decreased graft and patient survival Herpesvirus interactions: EBV/PTLD Indirect Effects […] CMV INFECTION Latent CMV infection Active CMV infection (viral replication) Direct effects Indirect effects […] CMV has the ability to down regulate MHC class 1 molecules.

• #54

  https://www.jpccr.eu/Cytomegalovirus-CMV-a-new-prospect-for-prevention,71451,0,2.html

  Human cytomegalovirus (HCMV), a member of the Betaherpesvirinae subfamily of the Herpesviridae family, is a widespread pathogen. […] CMV is a virus usually completely harmless to healthy people; nevertheless, it is still a major cause of morbidity and mortality in immunocompromised individuals, such as organ transplant recipients (also haematopoietic stem cell transplantation) and AIDS patients. […] Understanding the detailed construction of the virus helped to create exactly harmless virus strains used for research. […] Progress in genetics and biotechnology allowed the carrying out of changes in the virus genome. […] Today, we know the different parts of the DNA code, are able to modify them, delete, and add inserts. […] All these actions bring us closer to achieving the objective of an effective and safe vaccine.

• #55 Cytomegalovirus (CMV) Infection – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection

  In patients who are immunocompromised, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. […] Antivirals may help treat retinitis but are less effective when other organs are affected. […] Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antivirals to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease.

• #56 Cytomegalovirus | PPT

  https://www.slideshare.net/slideshow/cytomegalovirus-36882501/36882501

  CMV is still among the most important infectious complications after transplant. In the absence of prophylaxis, CMV reactivation can occur in over 75% of solid organ transplant recipients depending on other risk factors. Once CMV infection is established, then its replication is highly dynamic with rapid increases in viral load. CMV infection may lead to tissue invasive disease. […] CMV PATHOGENESIS Viral factors replication dynamics immune evasion viral heterogeneity viral co-infections Host factors CD4+, CD8+ T-cell NK cell, B-cell exogenous immunosuppression D/R immune status […] DIRECT EFFECTS OF CMV INFECTION CMV Viral Syndrome Fever, malaise, myalgias Leukopenia, thrombocytopenia, and other laboratory abnormalities Tissue Invasive Disease Hepatitis Pneumonitis Colitis Carditis Nephritis Pancreatitis Retinitis Direct Effects

• #57 Cytomegalovirus | PPT

  https://www.slideshare.net/slideshow/cytomegalovirus-36882501/36882501

  CMV is still among the most important infectious complications after transplant. In the absence of prophylaxis, CMV reactivation can occur in over 75% of solid organ transplant recipients depending on other risk factors. Once CMV infection is established, then its replication is highly dynamic with rapid increases in viral load. CMV infection may lead to tissue invasive disease. […] CMV PATHOGENESIS Viral factors replication dynamics immune evasion viral heterogeneity viral co-infections Host factors CD4+, CD8+ T-cell NK cell, B-cell exogenous immunosuppression D/R immune status […] DIRECT EFFECTS OF CMV INFECTION CMV Viral Syndrome Fever, malaise, myalgias Leukopenia, thrombocytopenia, and other laboratory abnormalities Tissue Invasive Disease Hepatitis Pneumonitis Colitis Carditis Nephritis Pancreatitis Retinitis Direct Effects

• #58 Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-aids-related-cytomegalovirus-retinitis

  Cytomegalovirus (CMV) retinitis is the most common serious ocular complication of acquired immunodeficiency syndrome (AIDS). The majority of disease is related to reactivation of latent infection. However, the introduction of potent combination antiretroviral therapy (ART) regimens in 1996 has led to changes in the incidence, natural history, management, and sequelae of CMV retinitis. […] The clinical manifestations, pathogenesis, risk factors, and diagnosis of CMV retinitis are discussed here. […] However, the introduction of potent combination ART has had a dramatic impact on CMV disease in the patient with human immunodeficiency virus (HIV). CMV disease essentially occurs only in patients with advanced immunosuppression, such as those who are either not receiving or have failed to respond to ART. […] In the era prior to the availability of potent ART regimens, the incidence of CMV retinitis was high.

• #59 Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis – UpToDate

  https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-aids-related-cytomegalovirus-retinitis

  Cytomegalovirus (CMV) retinitis is the most common serious ocular complication of acquired immunodeficiency syndrome (AIDS). The majority of disease is related to reactivation of latent infection. However, the introduction of potent combination antiretroviral therapy (ART) regimens in 1996 has led to changes in the incidence, natural history, management, and sequelae of CMV retinitis. […] The clinical manifestations, pathogenesis, risk factors, and diagnosis of CMV retinitis are discussed here. […] However, the introduction of potent combination ART has had a dramatic impact on CMV disease in the patient with human immunodeficiency virus (HIV). CMV disease essentially occurs only in patients with advanced immunosuppression, such as those who are either not receiving or have failed to respond to ART. […] In the era prior to the availability of potent ART regimens, the incidence of CMV retinitis was high.

• #60 Human cytomegalovirus (CMV) dysregulates neurodevelopmental pathways in cerebral organoids | Communications Biology

  https://www.nature.com/articles/s42003-024-05923-1

  Human cytomegalovirus (CMV) infection is the leading non-genetic aetiology of congenital malformation in developed countries, causing significant fetal neurological injury. This study investigated potential CMV pathogenetic mechanisms of fetal neural malformation using in vitro human cerebral organoids. Cerebral organoids were permissive to CMV replication, and infection dysregulated cellular pluripotency and differentiation pathways. Aberrant expression of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK), sonic hedgehog (SHH), pluripotency, neurodegeneration, axon guidance, hippo signalling and dopaminergic synapse pathways were observed in CMV-infected organoids using immunofluorescence and RNA-sequencing. Infection with CMV resulted in dysregulation of 236 Autism Spectrum Disorder (ASD)-related genes (p=1.57E-05) and pathways. This notable observation suggests potential links between congenital CMV infection and ASD. Cytomegalovirus infection-related dysregulation of key cerebral cellular pathways potentially provides important, modifiable pathogenetic mechanisms for congenital CMV-induced neural malformation and ASD.

• #61 Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

  https://eurekaselect.com/public/article/33900

  Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. […] The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. […] CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. […] This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus.

• #62 Congenital Cytomegalovirus Infection: Molecular Mechanisms Mediating Viral Pathogenesis

  https://eurekaselect.com/public/article/33900

  Human cytomegalovirus (CMV) is responsible for approximately 40,000 congenital infections in the United States each year. […] The mechanisms by which CMV injures the fetus are complex and likely include a combination of direct fetal injury induced by pathologic virally-encoded gene products, an inability of the maternal immune response to control infection, and the direct impact of infection on placental function. […] CMV encodes gene products that function, both at the RNA and the protein level, to interfere with many cellular processes. These include gene products that modify the cell cycle; interfere with apoptosis; induce an inflammatory response; mediate vascular injury; induce site-specific breakage of chromosomes; promote oncogenesis; dysregulate cellular proliferation; and facilitate evasion of host immune responses. […] This minireview summarizes current concepts regarding these aspects of the molecular virology of CMV and the potential pathogenic impact of viral gene expression on the developing fetus.

• #63 Human cytomegalovirus (CMV) dysregulates neurodevelopmental pathways in cerebral organoids | Communications Biology

  https://www.nature.com/articles/s42003-024-05923-1

  Human cytomegalovirus (CMV) infection is the leading non-genetic aetiology of congenital malformation in developed countries, causing significant fetal neurological injury. This study investigated potential CMV pathogenetic mechanisms of fetal neural malformation using in vitro human cerebral organoids. Cerebral organoids were permissive to CMV replication, and infection dysregulated cellular pluripotency and differentiation pathways. Aberrant expression of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK), sonic hedgehog (SHH), pluripotency, neurodegeneration, axon guidance, hippo signalling and dopaminergic synapse pathways were observed in CMV-infected organoids using immunofluorescence and RNA-sequencing. Infection with CMV resulted in dysregulation of 236 Autism Spectrum Disorder (ASD)-related genes (p=1.57E-05) and pathways. This notable observation suggests potential links between congenital CMV infection and ASD. Cytomegalovirus infection-related dysregulation of key cerebral cellular pathways potentially provides important, modifiable pathogenetic mechanisms for congenital CMV-induced neural malformation and ASD.

• #64 Human cytomegalovirus (CMV) dysregulates neurodevelopmental pathways in cerebral organoids | Communications Biology

  https://www.nature.com/articles/s42003-024-05923-1

  Human cytomegalovirus (CMV) infection is the leading non-genetic aetiology of congenital malformation in developed countries, causing significant fetal neurological injury. This study investigated potential CMV pathogenetic mechanisms of fetal neural malformation using in vitro human cerebral organoids. Cerebral organoids were permissive to CMV replication, and infection dysregulated cellular pluripotency and differentiation pathways. Aberrant expression of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK), sonic hedgehog (SHH), pluripotency, neurodegeneration, axon guidance, hippo signalling and dopaminergic synapse pathways were observed in CMV-infected organoids using immunofluorescence and RNA-sequencing. Infection with CMV resulted in dysregulation of 236 Autism Spectrum Disorder (ASD)-related genes (p=1.57E-05) and pathways. This notable observation suggests potential links between congenital CMV infection and ASD. Cytomegalovirus infection-related dysregulation of key cerebral cellular pathways potentially provides important, modifiable pathogenetic mechanisms for congenital CMV-induced neural malformation and ASD.

• #65 Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03276-4

  Maternal administration of ASA during pregnancy improved CMV-related neurodevelopmental abnormalities in the offspring after infection of the rat fetal brain, likely through Cox-1 related and Cox-1 unrelated modes of action. […] The involvement of early altered cellular and molecular immune processes in the neuropathogenesis of congenital CMV infection has been increasingly questioned in the recent years. […] In this model, we also show that maternal intake during pregnancy of ASA, a drug known to inhibit the PG pathway, reverted the Cox-1 overexpression seen in fetal microglia, improved postnatal survival and the severity of the postnatal neurologic phenotypes, and prevented against the epileptiform events recorded in neocortical slices from CMV-infected pups. […] The possible role of the PG pathway in the neuropathogenesis of congenital CMV infection had not been questioned in vivo yet.

• #66 Cytomegalovirus infection of the fetal brain: intake of aspirin during pregnancy blunts neurodevelopmental pathogenesis in the offspring | Journal of Neuroinflammation | Full Text

  https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-024-03276-4

  The increased amounts of PGE2 and the increased proportions of microglial cells expressing Cox-1 or Cox-2 detected here in the CMV-infected brains, as well as the beneficial effects of ASA, are consistent with the known and central role of the PG pathway in neuroinflammation, in microglia homeostasis, and in viral infections. […] In summary, whereas no improvement of the postnatal epileptic outcome of CMV infection was obtained in vivo in Cox-1 KO pups, an undisputable beneficial effect of Cox-1 KO on the epileptiform events was obtained ex vivo as with ASA in neocortices from CMV-infected pups.

• #67 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Viruses with pathogen specific epitopes with similarity to the host might activate auto reactive lymphocytes, which is termed molecular mimicry. Transfer of viral specific epitopes to the host then initiates the process of disease pathogenesis. […] Mitigation of the autoimmune process by viral infections can also occur, particularly if there is repeated infection by the same viral strain. Viruses can attract potentially injurious T cells towards the infection by release of chemokines, which decreases the likelihood of autoantibody production. T regulatory cells(TREG cells) when activated, may help to lessen the autoimmune processes. […] Specific epitope targeted expansion of CD8+ T cells,in response to CMV is not typical of other viral infections. CMV has been associated with many autoimmune diseases, and there has been a higher prevalence of autoimmune disease among patients with CMV infection described. The immune profile among seropositive CMV autoimmune disease patients includes the proliferation of CD4+/CD28 null T cells. CD4+ CD28 null population is three fold higher among CMV positive rheumatoid arthritis patients compared with healthy CMV positive patients. This increase may be a marker for disease pathogenesis and progression. A previous study has shown that CMV specific CD4+CD 28 null cells are regulatory T cells.

• #68 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Autoimmune Diseases and in particular Systemic Lupus Erythematosis (SLE) are associated with responses to viral antigenemia. The mechanisms by which the virus and autoimmune disease are related include disease activation, mitigation and susceptibility of the host to the viral infection during exacerbations of autoimmune disease. This paper will review the cellular, molecular and disease associations between SLE and Cytomegalovirus infection. […] Viruses, like other microbial agents may be integral triggering factors in the development of autoimmune disease. Many specific viruses have been implicated in the modulation of local and systemic environmental factors that lead to the formulation of organ specific and circulating autoantibodies. Direct infection may activate an immune response by cross reaction between carbohydrate, proteins, peptides or nucleic acids of the pathogen and the hosts molecular structural receptors.

• #69 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Viruses with pathogen specific epitopes with similarity to the host might activate auto reactive lymphocytes, which is termed molecular mimicry. Transfer of viral specific epitopes to the host then initiates the process of disease pathogenesis. […] Mitigation of the autoimmune process by viral infections can also occur, particularly if there is repeated infection by the same viral strain. Viruses can attract potentially injurious T cells towards the infection by release of chemokines, which decreases the likelihood of autoantibody production. T regulatory cells(TREG cells) when activated, may help to lessen the autoimmune processes. […] Specific epitope targeted expansion of CD8+ T cells,in response to CMV is not typical of other viral infections. CMV has been associated with many autoimmune diseases, and there has been a higher prevalence of autoimmune disease among patients with CMV infection described. The immune profile among seropositive CMV autoimmune disease patients includes the proliferation of CD4+/CD28 null T cells. CD4+ CD28 null population is three fold higher among CMV positive rheumatoid arthritis patients compared with healthy CMV positive patients. This increase may be a marker for disease pathogenesis and progression. A previous study has shown that CMV specific CD4+CD 28 null cells are regulatory T cells.

• #70 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Autoimmune Diseases and in particular Systemic Lupus Erythematosis (SLE) are associated with responses to viral antigenemia. The mechanisms by which the virus and autoimmune disease are related include disease activation, mitigation and susceptibility of the host to the viral infection during exacerbations of autoimmune disease. This paper will review the cellular, molecular and disease associations between SLE and Cytomegalovirus infection. […] Viruses, like other microbial agents may be integral triggering factors in the development of autoimmune disease. Many specific viruses have been implicated in the modulation of local and systemic environmental factors that lead to the formulation of organ specific and circulating autoantibodies. Direct infection may activate an immune response by cross reaction between carbohydrate, proteins, peptides or nucleic acids of the pathogen and the hosts molecular structural receptors.

• #71 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Viruses with pathogen specific epitopes with similarity to the host might activate auto reactive lymphocytes, which is termed molecular mimicry. Transfer of viral specific epitopes to the host then initiates the process of disease pathogenesis. […] Mitigation of the autoimmune process by viral infections can also occur, particularly if there is repeated infection by the same viral strain. Viruses can attract potentially injurious T cells towards the infection by release of chemokines, which decreases the likelihood of autoantibody production. T regulatory cells(TREG cells) when activated, may help to lessen the autoimmune processes. […] Specific epitope targeted expansion of CD8+ T cells,in response to CMV is not typical of other viral infections. CMV has been associated with many autoimmune diseases, and there has been a higher prevalence of autoimmune disease among patients with CMV infection described. The immune profile among seropositive CMV autoimmune disease patients includes the proliferation of CD4+/CD28 null T cells. CD4+ CD28 null population is three fold higher among CMV positive rheumatoid arthritis patients compared with healthy CMV positive patients. This increase may be a marker for disease pathogenesis and progression. A previous study has shown that CMV specific CD4+CD 28 null cells are regulatory T cells.

• #72 Cytomegalovirus (CMV) Infection: A Role in the Pathogenesis of Systemic Lupus Erythematosis (SLE)

  https://www.sciforschenonline.org/journals/autoimmune-infectious/AIDOA-2-115.php

  Viruses with pathogen specific epitopes with similarity to the host might activate auto reactive lymphocytes, which is termed molecular mimicry. Transfer of viral specific epitopes to the host then initiates the process of disease pathogenesis. […] Mitigation of the autoimmune process by viral infections can also occur, particularly if there is repeated infection by the same viral strain. Viruses can attract potentially injurious T cells towards the infection by release of chemokines, which decreases the likelihood of autoantibody production. T regulatory cells(TREG cells) when activated, may help to lessen the autoimmune processes. […] Specific epitope targeted expansion of CD8+ T cells,in response to CMV is not typical of other viral infections. CMV has been associated with many autoimmune diseases, and there has been a higher prevalence of autoimmune disease among patients with CMV infection described. The immune profile among seropositive CMV autoimmune disease patients includes the proliferation of CD4+/CD28 null T cells. CD4+ CD28 null population is three fold higher among CMV positive rheumatoid arthritis patients compared with healthy CMV positive patients. This increase may be a marker for disease pathogenesis and progression. A previous study has shown that CMV specific CD4+CD 28 null cells are regulatory T cells.

• #73 Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006202

  Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. […] We hypothesized that persistent CMV replication in the intestinal epithelium of HIV/CMV-coinfected individuals impairs gut epithelial barrier function. […] Independent of HIV, CMV disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. […] The effect of CMV infection on the intestinal epithelium is mediated, at least in part, by the CMV-induced proinflammatory cytokine IL-6. […] Taken together, these observations underscore a novel way to prevent and treat gut epithelial barrier dysfunction in HIV infection.

• #74 Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006202

  We found that independent of HIV, CMV disrupts tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance (TER), a measure of epithelial monolayer integrity, and enhancing epithelial barrier permeability. […] Our results support a potentially active role for CMV in driving epithelial barrier dysfunction and microbial translocation. […] These observations suggest that CMV reactivation in the gastrointestinal epithelium of HIV-infected individuals could be a potent cofactor that stimulates release of proinflammatory cytokines from intestinal epithelial cells, compromising barrier function and locally initiating bacterial translocation that leads to chronic inflammation in the gut.

• #75 Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006202

  Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. […] We hypothesized that persistent CMV replication in the intestinal epithelium of HIV/CMV-coinfected individuals impairs gut epithelial barrier function. […] Independent of HIV, CMV disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. […] The effect of CMV infection on the intestinal epithelium is mediated, at least in part, by the CMV-induced proinflammatory cytokine IL-6. […] Taken together, these observations underscore a novel way to prevent and treat gut epithelial barrier dysfunction in HIV infection.

• #76 Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006202

  Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. […] We hypothesized that persistent CMV replication in the intestinal epithelium of HIV/CMV-coinfected individuals impairs gut epithelial barrier function. […] Independent of HIV, CMV disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. […] The effect of CMV infection on the intestinal epithelium is mediated, at least in part, by the CMV-induced proinflammatory cytokine IL-6. […] Taken together, these observations underscore a novel way to prevent and treat gut epithelial barrier dysfunction in HIV infection.

• #77 Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006202

  We found that independent of HIV, CMV disrupts tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance (TER), a measure of epithelial monolayer integrity, and enhancing epithelial barrier permeability. […] Our results support a potentially active role for CMV in driving epithelial barrier dysfunction and microbial translocation. […] These observations suggest that CMV reactivation in the gastrointestinal epithelium of HIV-infected individuals could be a potent cofactor that stimulates release of proinflammatory cytokines from intestinal epithelial cells, compromising barrier function and locally initiating bacterial translocation that leads to chronic inflammation in the gut.

• #78

  https://www.jci.org/articles/view/45449

  However, these results do not rule out other sites of latency. […] A particularly intriguing one of these is an alternatively spliced, latency-associated form of cmvIL-10 (LAcmvIL-10), which retains some but not all of the activities of cmvIL-10. […] The common manifestations of CMV infection depend to a large extent on the particular clinical setting. […] Overt disease is limited primarily to patients with significant immune system dysfunction that can result from other illnesses or iatrogenic causes. […] Current therapies. Ganciclovir, foscarnet, and cidofovir are currently available drugs for CMV treatment and prevention. […] Drug resistance can develop with all available drugs. […] The development of vaccines has been a primary goal for controlling CMV. […] However, many questions remain about the functions of numerous CMV genes, the mechanism of latency, and the pathogenetic processes that account for differing disease manifestations in various clinical settings.

• #79 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  CMV replicates within endothelial cells at a slow rate. Like other herpesviruses, CMV expresses genes in a temporally controlled manner. […] Synthesis of the viral double-stranded DNA genome occurs in the host cell nucleus within specialized viral replication compartments. […] The prognosis for most patients with CMV is good as long as they do not have a state of immunosuppression. Recovery is usually complete with treatment. However, fatigue may persist for several months. […] CMV can affect almost any organ in the body, and hence an interprofessional approach is necessary. Patients who are immunocompromised may be considered prophylaxis therapy. […] Anti-CMV drugs target the viral DNA polymerase, pUL54. […] Two CMV proteins are implicated in the resistance of these drugs: pUL97 and pUL54.

• #80 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  CMV replicates within endothelial cells at a slow rate. Like other herpesviruses, CMV expresses genes in a temporally controlled manner. […] Synthesis of the viral double-stranded DNA genome occurs in the host cell nucleus within specialized viral replication compartments. […] The prognosis for most patients with CMV is good as long as they do not have a state of immunosuppression. Recovery is usually complete with treatment. However, fatigue may persist for several months. […] CMV can affect almost any organ in the body, and hence an interprofessional approach is necessary. Patients who are immunocompromised may be considered prophylaxis therapy. […] Anti-CMV drugs target the viral DNA polymerase, pUL54. […] Two CMV proteins are implicated in the resistance of these drugs: pUL97 and pUL54.

• #81

  https://www.jci.org/articles/view/45449

  However, these results do not rule out other sites of latency. […] A particularly intriguing one of these is an alternatively spliced, latency-associated form of cmvIL-10 (LAcmvIL-10), which retains some but not all of the activities of cmvIL-10. […] The common manifestations of CMV infection depend to a large extent on the particular clinical setting. […] Overt disease is limited primarily to patients with significant immune system dysfunction that can result from other illnesses or iatrogenic causes. […] Current therapies. Ganciclovir, foscarnet, and cidofovir are currently available drugs for CMV treatment and prevention. […] Drug resistance can develop with all available drugs. […] The development of vaccines has been a primary goal for controlling CMV. […] However, many questions remain about the functions of numerous CMV genes, the mechanism of latency, and the pathogenetic processes that account for differing disease manifestations in various clinical settings.

• #82 Cytomegalovirus (CMV) Histology and Pathology: Understanding the

  https://www.longdom.org/open-access/cytomegalovirus-cmv-histology-and-pathology-understanding-the-viruss-impact-on-human-cells-1100648.html

  CMV infection can cause the formation of giant cells, which are large, multinucleated cells that arise from the fusion of infected cells. […] CMV infection can induce an inflammatory response, characterized by infiltrates of immune cells, such as lymphocytes and macrophages. […] The pathology of CMV infection is diverse and can affect various organs and tissues. […] CMV infection can cause hepatitis, liver failure and cirrhosis. […] CMV infection can cause encephalitis, meningitis and cognitive impairment. […] CMV infection can cause retinitis, uveitis and vision loss. […] Treatment for CMV infection usually involves antiviral therapy with medications such as ganciclovir or valganciclovir. […] Understanding these changes is essential for diagnosing and treating CMV infections, particularly in immunocompromised individuals where the virus can have severe consequences. Further study into the molecular mechanisms underlying CMV pathogenesis may lead to the development of more effective therapies and ultimately improve patient outcomes.

• #83 Cytomegalovirus (CMV) Infection – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection

  In patients who are immunocompromised, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. […] Antivirals may help treat retinitis but are less effective when other organs are affected. […] Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antivirals to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease.

• #84 Cytomegalovirus (CMV) Infection – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection

  In patients who are immunocompromised, CMV is a major cause of morbidity and mortality. Disease often results from reactivation of latent virus. The lungs, gastrointestinal tract, or CNS may be involved. […] Antivirals may help treat retinitis but are less effective when other organs are affected. […] Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antivirals to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease.

• #85 About Cytomegalovirus | Cytomegalovirus (CMV) and Congenital CMV Infection | CDC

  https://www.cdc.gov/cytomegalovirus/about/index.html

  CMV is the most common infectious cause of birth defects in the United States. It can spread through body fluids like saliva and urine, especially by children. […] Once CMV is in a persons body, it stays there for life and can reactivate. A person can also be re-infected with a different strain of the virus. […] If you have a weakened immune system and get CMV, you can have more serious symptoms affecting the eyes; lungs; liver; esophagus; stomach; and intestines. […] Medications called antivirals are available to treat: CMV infection in people who have weakened immune systems. […] Valganciclovir is an antiviral that might improve hearing and developmental outcomes in babies. It can have serious side effects and has only been studied in babies with signs of congenital CMV infection.

• #86

  https://www.jci.org/articles/view/45449

  However, these results do not rule out other sites of latency. […] A particularly intriguing one of these is an alternatively spliced, latency-associated form of cmvIL-10 (LAcmvIL-10), which retains some but not all of the activities of cmvIL-10. […] The common manifestations of CMV infection depend to a large extent on the particular clinical setting. […] Overt disease is limited primarily to patients with significant immune system dysfunction that can result from other illnesses or iatrogenic causes. […] Current therapies. Ganciclovir, foscarnet, and cidofovir are currently available drugs for CMV treatment and prevention. […] Drug resistance can develop with all available drugs. […] The development of vaccines has been a primary goal for controlling CMV. […] However, many questions remain about the functions of numerous CMV genes, the mechanism of latency, and the pathogenetic processes that account for differing disease manifestations in various clinical settings.

• #87

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Human cytomegalovirus (HCMV) infection remains a significant global health challenge, particularly for immunocompromised individuals and newborns. This comprehensive review synthesizes current knowledge on HCMV pathogenesis, prevention, and treatment strategies. We examine the molecular mechanisms of HCMV entry, focusing on the structure and function of key envelope glycoproteins (gB, gH/gL/gO, gH/gL/pUL128-131) and their interactions with cellular receptors such as PDGFR, NRP2, and THBD. […] The review explores HCMVs sophisticated immune evasion strategies, including interference with pattern recognition receptor signaling, modulation of antigen presentation, and regulation of NK and T cell responses. […] Recent years have witnessed remarkable advances in our understanding of HCMV biology and pathogenesis, driven by technological breakthroughs in structural biology, immunology, and molecular virology. High-resolution structural studies have revealed the intricate architecture of viral glycoprotein complexes and their interactions with host cell receptors.

• #88 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #89 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #90 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #91 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #92 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #93 The Bumpy Road to a Cytomegalovirus Vaccine – The Native Antigen Company

  https://thenativeantigencompany.com/the-bumpy-road-to-a-cytomegalovirus-vaccine/

  The current DISC frontrunner is Merck’s V160 strain, which includes rapamycin-binding protein (RBP) insertion. […] The protein responsible for mediating CMV’s entry to human cells and the dominant target of the body’s humoral response is glycoprotein B (gB). […] A vaccine will need to stimulate both the humoral and cell-mediated immune responses, as anti-CMV antibodies have been shown to prevent transmission and minimize clinical manifestations, while T-cells are likely involved in suppressing viral replication and preventing reactivation of infection. […] Immunization is also challenged by the fact that natural infection with CMV is only partially protective and does not prevent placental transmission of the virus. […] mRNA technologies, such as Moderna’s, are entirely cell-free and avoid the need for complex manufacturing processes, which would make these strategies much more practical for real-world use. […] Despite these challenges, the industry remains optimistic. Successful phase III trials from vaccine front-runners, such as V160 and mRNA-1647, could clear the path to market in the coming years.

• #94 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  CMV replicates within endothelial cells at a slow rate. Like other herpesviruses, CMV expresses genes in a temporally controlled manner. […] Synthesis of the viral double-stranded DNA genome occurs in the host cell nucleus within specialized viral replication compartments. […] The prognosis for most patients with CMV is good as long as they do not have a state of immunosuppression. Recovery is usually complete with treatment. However, fatigue may persist for several months. […] CMV can affect almost any organ in the body, and hence an interprofessional approach is necessary. Patients who are immunocompromised may be considered prophylaxis therapy. […] Anti-CMV drugs target the viral DNA polymerase, pUL54. […] Two CMV proteins are implicated in the resistance of these drugs: pUL97 and pUL54.

• #95 Cytomegalovirus – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK459185/

  CMV replicates within endothelial cells at a slow rate. Like other herpesviruses, CMV expresses genes in a temporally controlled manner. […] Synthesis of the viral double-stranded DNA genome occurs in the host cell nucleus within specialized viral replication compartments. […] The prognosis for most patients with CMV is good as long as they do not have a state of immunosuppression. Recovery is usually complete with treatment. However, fatigue may persist for several months. […] CMV can affect almost any organ in the body, and hence an interprofessional approach is necessary. Patients who are immunocompromised may be considered prophylaxis therapy. […] Anti-CMV drugs target the viral DNA polymerase, pUL54. […] Two CMV proteins are implicated in the resistance of these drugs: pUL97 and pUL54.

• #96

  https://www.jci.org/articles/view/45449

  However, these results do not rule out other sites of latency. […] A particularly intriguing one of these is an alternatively spliced, latency-associated form of cmvIL-10 (LAcmvIL-10), which retains some but not all of the activities of cmvIL-10. […] The common manifestations of CMV infection depend to a large extent on the particular clinical setting. […] Overt disease is limited primarily to patients with significant immune system dysfunction that can result from other illnesses or iatrogenic causes. […] Current therapies. Ganciclovir, foscarnet, and cidofovir are currently available drugs for CMV treatment and prevention. […] Drug resistance can develop with all available drugs. […] The development of vaccines has been a primary goal for controlling CMV. […] However, many questions remain about the functions of numerous CMV genes, the mechanism of latency, and the pathogenetic processes that account for differing disease manifestations in various clinical settings.

• #97

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Human cytomegalovirus (HCMV) infection remains a significant global health challenge, particularly for immunocompromised individuals and newborns. This comprehensive review synthesizes current knowledge on HCMV pathogenesis, prevention, and treatment strategies. We examine the molecular mechanisms of HCMV entry, focusing on the structure and function of key envelope glycoproteins (gB, gH/gL/gO, gH/gL/pUL128-131) and their interactions with cellular receptors such as PDGFR, NRP2, and THBD. […] The review explores HCMVs sophisticated immune evasion strategies, including interference with pattern recognition receptor signaling, modulation of antigen presentation, and regulation of NK and T cell responses. […] Recent years have witnessed remarkable advances in our understanding of HCMV biology and pathogenesis, driven by technological breakthroughs in structural biology, immunology, and molecular virology. High-resolution structural studies have revealed the intricate architecture of viral glycoprotein complexes and their interactions with host cell receptors.

• #98

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  Human cytomegalovirus (HCMV) infection remains a significant global health challenge, particularly for immunocompromised individuals and newborns. This comprehensive review synthesizes current knowledge on HCMV pathogenesis, prevention, and treatment strategies. We examine the molecular mechanisms of HCMV entry, focusing on the structure and function of key envelope glycoproteins (gB, gH/gL/gO, gH/gL/pUL128-131) and their interactions with cellular receptors such as PDGFR, NRP2, and THBD. […] The review explores HCMVs sophisticated immune evasion strategies, including interference with pattern recognition receptor signaling, modulation of antigen presentation, and regulation of NK and T cell responses. […] Recent years have witnessed remarkable advances in our understanding of HCMV biology and pathogenesis, driven by technological breakthroughs in structural biology, immunology, and molecular virology. High-resolution structural studies have revealed the intricate architecture of viral glycoprotein complexes and their interactions with host cell receptors.

• #99

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  These insights have opened new avenues for therapeutic intervention, including the development of novel antiviral compounds, vaccines, and immunotherapeutic approaches. […] HCMV possesses the largest genome among known human DNA viruses, spanning approximately 235250 kb and encoding over 170 proteins and featuring a complex virion structure consisting of a nucleocapsid, tegument layer, and glycoprotein-studded envelope. […] The HCMV life cycle is characterized by a temporal cascade of gene expression, categorized into immediate early (IE), early (E), and late (L) genes. […] HCMV can establish latency in certain cell types, particularly in CD34+ hematopoietic progenitor cells and CD14+ monocytes. […] During latency, viral gene expression is highly restricted, with only a subset of viral transcripts, including latency-associated transcripts, being expressed.

• #100

  https://www.jci.org/articles/view/45449

  Human cytomegalovirus (CMV), one of the eight herpesviruses that commonly infect humans, is best known for its propensity to cause disease in immunocompromised patients, especially transplant recipients, patients with advanced AIDS, and congenitally infected newborns. […] Advances in molecular virology coupled with improvements in diagnostic methods and treatment options have vastly improved our understanding of and ability to manage CMV, but many uncertainties remain, including the mechanisms of persistence and pathogenesis and its hypothesized roles in a variety of human illnesses. […] Understanding the pathogenesis of CMV diseases remains an enormous challenge, in large part because the virus only grows in human cells and it differs substantially from even its primate-infecting cousins.

• #101

  https://link.springer.com/article/10.1186/s43556-024-00226-7

  The gH/gL complex is a key component in the entry process, directly binding integrin 1 and altering normal intracellular Akt signaling, sustaining viral survival and persistence. […] HCMV has evolved sophisticated mechanisms to evade host immune responses, targeting both innate and adaptive immunity. […] HCMV encodes multiple proteins and microRNAs to target and inhibit PRR signaling pathways, which is a key strategy for viral evasion of innate immune recognition. […] The IFN-I system is a key defense line against viral infections, and HCMV has evolved multiple strategies to suppress IFN-I production and signaling. […] HCMV employs various strategies to modulate DC function, indirectly regulating T and B cell responses. […] Overall, the field of HCMV research is at an exciting juncture, with new molecular and structural insights driving the development of innovative therapeutic strategies.

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