Materiały źródłowe

• #1 Herpes Simplex: Background, Microbiology, Pathophysiology

  https://emedicine.medscape.com/article/218580-overview

  Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease, whereas HSV-2 is traditionally associated with genital disease. Lesion location, however, is not necessarily indicative of viral type, as HSV-1 is associated with genital infections more often than HSV-2 in some unique subpopulations. […] HSV belongs to the alpha herpesvirus group. It is an enveloped virus that is approximately 160 nm in diameter with a linear, double-stranded DNA genome. The overall sequence homology between HSV-1 and HSV-2 is about 50%. HSV-1 has tropism for oral epithelium, while HSV-2 has tropism for genital epithelium. HSV infection is mediated through attachment via ubiquitous receptors to cells, including sensory neurons, leading to establishment of latency.

• #2 Cold sore – Wikipedia

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

  A cold sore is a type of herpes infection caused by the herpes simplex virus that affects primarily the lip. […] The cause is usually herpes simplex virus type 1 (HSV-1) and occasionally herpes simplex virus type 2 (HSV-2). […] Cold sores are the result of the virus reactivating in the body. Once HSV-1 has entered the body, it never leaves. The virus moves from the mouth to remain latent in the central nervous system. In approximately one-third of people, the virus can „wake up” or reactivate to cause disease. When reactivation occurs, the virus travels down the nerves to the skin where it may cause blisters (cold sores) around the lips or mouth area. […] Cold sore outbreaks may be influenced by stress, menstruation, sunlight, sunburn, fever, dehydration, or local skin trauma. […] The body’s immune system typically fights the virus.

• #3 Herpes Simplex: Background, Microbiology, Pathophysiology

  https://emedicine.medscape.com/article/218580-overview

  Herpes simplex viruses are ubiquitous, host-adapted pathogens that cause a wide variety of disease states. Two types exist: herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Both are closely related but differ in epidemiology. HSV-1 is traditionally associated with orofacial disease, whereas HSV-2 is traditionally associated with genital disease. Lesion location, however, is not necessarily indicative of viral type, as HSV-1 is associated with genital infections more often than HSV-2 in some unique subpopulations. […] HSV belongs to the alpha herpesvirus group. It is an enveloped virus that is approximately 160 nm in diameter with a linear, double-stranded DNA genome. The overall sequence homology between HSV-1 and HSV-2 is about 50%. HSV-1 has tropism for oral epithelium, while HSV-2 has tropism for genital epithelium. HSV infection is mediated through attachment via ubiquitous receptors to cells, including sensory neurons, leading to establishment of latency.

• #4 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. […] The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #5 Herpes Simplex: Background, Microbiology, Pathophysiology

  https://emedicine.medscape.com/article/218580-overview

  Cellular immunity is an important defense against herpes simplex. Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals with AIDS. Herpes simplex infection can also complicate burn wounds or damaged skin such as in atopic dermatitis or other allergic dermatoses. […] HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare.

• #6 Herpes: Symptoms, Causes, Treatment, and More

  https://www.healthline.com/health/herpes-simplex

  HSV is a contagious virus that can be transmitted through direct contact with sores. […] That said, since the virus also sheds on a small percentage of days, it’s possible to transmit or contract HSV even when symptoms aren’t present. In fact, many people contract HSV from people who don’t know they have the virus. […] If you develop HSV, your body produces particles of virus that you can transmit to others. The virus sheds from sores during an episode, but it also sheds at other times when you have no sores or obvious symptoms. You may not even know you have HSV. Some research suggests shedding happens on: […] You can transmit or contract HSV-1, or oral herpes, through direct contact with a herpes sore, saliva, or other bodily secretions during an episode. If you’re shedding the virus, someone can contract it through direct contact with the site of the infection.

• #7 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #8

  https://link.springer.com/article/10.1007/s007050050030

  Murine flank scarification with HSV-1 and -2 results in primary lesions at the site of inoculation within three days and lesions at secondary sites within four days. […] Using this model, we investigated the role of the epidermal basement membrane in HSV pathogenesis. […] In contrast, intradermal injection of HSV below the epidermal basement membrane did not cause disease. […] These data suggest that the basement membrane is a barrier to the passage and spread of HSV.

• #9 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #10 Reddit – The heart of the internet

  https://www.reddit.com/r/science/comments/28vuzr/science_ama_series_iama_virologist_who_studies/

  The virus infects mucosal epithelial (skin) cells and replicates, destroying the cells and causing lesions. […] New virus enters into the nerve endings nearby and travels to the body of the neuron. Here it will become silent, ever waiting until . . . […] The virus reactivates! It will replicate in the neuron, travel back to the nerve ending, and re-infect the same site of the initial infection – and then maybe someone else.

• #11 Reddit – The heart of the internet

  https://www.reddit.com/r/science/comments/28vuzr/science_ama_series_iama_virologist_who_studies/

  The virus infects mucosal epithelial (skin) cells and replicates, destroying the cells and causing lesions. […] New virus enters into the nerve endings nearby and travels to the body of the neuron. Here it will become silent, ever waiting until . . . […] The virus reactivates! It will replicate in the neuron, travel back to the nerve ending, and re-infect the same site of the initial infection – and then maybe someone else.

• #12

  https://grantome.com/grant/NIH/R01-AI148478-02

  Herpesviruses are associated with a variety of disease in the human host, ranging from asymptomatic infections to life threatening disease, including encephalitis and cancer. […] HSV-1 serves as a prototypic herpesvirus family member and provides an ideal model to understand the requirements for virus infection since it replicates well in cell culture and many reagents have been developed for its study. […] Herpesvirus entry into cells requires fusion of the outer envelope of the virus with a cell membrane. Spread of infection can occur via infectious virus or virus-induced cell fusion. The ultimate objective of studies described here is to understand how herpesviruses, specifically HSV-1, induce membrane fusion, the process required for viral entry and cell fusion. Requirements for HSV-induced membrane fusion include the coordinated activities of four HSV glycoproteins (gD, the hererodimeric gHgL complex, and gB) and specific cellular receptors. Our central hypothesis is that gD, present in the viral envelope or on an infected cell surface, binds to a cellular receptor, such as nectin-1, on an uninfected cell and activates gHgL and gB via protein-protein interactions, resulting in fusion mediated by gB. […] The results of these studies will lead to an understanding of the mechanism of herpesvirus-induced membrane fusion and to new approaches for the prevention and treatment of herpesvirus infections.

• #13

  https://grantome.com/grant/NIH/R01-AI148478-02

  Herpesviruses are associated with a variety of disease in the human host, ranging from asymptomatic infections to life threatening disease, including encephalitis and cancer. […] HSV-1 serves as a prototypic herpesvirus family member and provides an ideal model to understand the requirements for virus infection since it replicates well in cell culture and many reagents have been developed for its study. […] Herpesvirus entry into cells requires fusion of the outer envelope of the virus with a cell membrane. Spread of infection can occur via infectious virus or virus-induced cell fusion. The ultimate objective of studies described here is to understand how herpesviruses, specifically HSV-1, induce membrane fusion, the process required for viral entry and cell fusion. Requirements for HSV-induced membrane fusion include the coordinated activities of four HSV glycoproteins (gD, the hererodimeric gHgL complex, and gB) and specific cellular receptors. Our central hypothesis is that gD, present in the viral envelope or on an infected cell surface, binds to a cellular receptor, such as nectin-1, on an uninfected cell and activates gHgL and gB via protein-protein interactions, resulting in fusion mediated by gB. […] The results of these studies will lead to an understanding of the mechanism of herpesvirus-induced membrane fusion and to new approaches for the prevention and treatment of herpesvirus infections.

• #14 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #15 How herpes seizes proteins’ means of production | EMBL

  https://www.embl.org/news/science/how-herpes-seizes-proteins-means-of-production/

  Scientists at EMBL Hamburg helped to reveal how the herpes simplex virus hijacks human proteins. […] The Graham and Crump groups at the University of Cambridge and the Svergun Group at EMBL Hamburg have discovered a mechanism by which the herpes simplex virus takes control of the molecular machinery of human cells. Their work reveals how a dedicated viral protein hijacks key host proteins, forcing the host cell to produce and release copies of the virus. […] Like other viruses, HSV-1 multiplies by hijacking the molecular machinery of infected human cells. The infected cell starts to produce copies of the virus, which then use the cells secretory system to exit the host cell and infect other cells. […] One of the steps required for virus replication is the production of viral proteins. To ensure all parts of the molecular machinery work in synchrony, cells have dedicated production managers proteins that switch other proteins on and off when needed.

• #16 Herpes simplex virus – Wikipedia

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

  HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. […] After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron’s axon to the skin, where virus replication and shedding occur and may cause new sores. […] HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking the transporter associated with antigen processing (TAP) induced by the secretion of ICP-47 by HSV. […] Following the infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced. […] The early proteins transcribed are used in the regulation of genetic replication of the virus.

• #17 Herpes simplex virus – Wikipedia

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

  HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. […] After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron’s axon to the skin, where virus replication and shedding occur and may cause new sores. […] HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking the transporter associated with antigen processing (TAP) induced by the secretion of ICP-47 by HSV. […] Following the infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced. […] The early proteins transcribed are used in the regulation of genetic replication of the virus.

• #18 June 13, 2019 | Scientists reveal DNA packaging mechanism of HSV-1, the virus that causes cold sores – California NanoSystems Institute

  https://cnsi.ucla.edu/june-13-2019-scientists-reveal-dna-packaging-mechanism-of-hsv-1-the-virus-that-causes-cold-sores/

  A new technique developed by researchers from the California NanoSystems Institute at UCLA has allowed them to become the first scientists to clearly see the intricate machinery responsible for compressing DNA into the small interior shell, or capsid, of herpes simplex virus type 1, or HSV-1, the virus responsible for causing cold sores. […] The DNA packaging process in herpesviruses is fascinating because it’s driven by a nanoscale motor that pumps the viral capsid full of DNA under incredible pressure, up to internal pressures of tens of atmospheres. […] Despite being of critical importance, the details of this DNA packaging process were previously not well understood, largely due to the difficulty of visualizing the unique components of the virus at sufficient resolution. […] This work represents the first detailed look at the structure of the portal vertex and the first atomic model of its constituent portal complex in the HSV-1 virus.

• #19 Reddit – The heart of the internet

  https://www.reddit.com/r/science/comments/28vuzr/science_ama_series_iama_virologist_who_studies/

  The virus infects mucosal epithelial (skin) cells and replicates, destroying the cells and causing lesions. […] New virus enters into the nerve endings nearby and travels to the body of the neuron. Here it will become silent, ever waiting until . . . […] The virus reactivates! It will replicate in the neuron, travel back to the nerve ending, and re-infect the same site of the initial infection – and then maybe someone else.

• #20 Herpes simplex virus – Wikipedia

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

  HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. […] After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron’s axon to the skin, where virus replication and shedding occur and may cause new sores. […] HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking the transporter associated with antigen processing (TAP) induced by the secretion of ICP-47 by HSV. […] Following the infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced. […] The early proteins transcribed are used in the regulation of genetic replication of the virus.

• #21 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. […] The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #22 HSV-1 AND 2: Pathogenesis and disease (Chapter 32) – Human Herpesviruses

  https://www.cambridge.org/core/books/human-herpesviruses/hsv1-and-2-pathogenesis-and-disease/C6C9E1332042876CBFDA6DEEE5B5C89B

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #23 Treatment and prevention of herpes simplex virus type 1 in immunocompetent adolescents and adults – UpToDate

  https://www.uptodate.com/contents/treatment-and-prevention-of-herpes-simplex-virus-type-1-in-immunocompetent-adolescents-and-adults

  Herpes simplex virus type 1 (HSV-1) is a cause of recurrent vesiculoulcerative lesions of the oral or genital mucosa. It can also cause infection in the eye, skin, central nervous system, and/or visceral organs. […] The management of HSV-1 infection in the immunocompetent host depends upon a variety of considerations, including: Whether the patient has primary HSV-1 infection or reactivation disease, the severity of symptoms, the site of infection (eg, mucosal versus disseminated disease), the frequency of recurrences. Antiviral agents for HSV infection include acyclovir, valacyclovir, and famciclovir. Metabolites of these nucleoside derivatives interfere with the synthesis of viral DNA by inhibiting viral DNA polymerase. […] Oral HSV-1 recurrences occur when the virus reactivates from the trigeminal sensory ganglion, where it persists in a latent state. Symptomatic reactivation leads to oral herpes („cold sores”), which occur along the vermillion border of the lips.

• #24 HSV-1 AND 2: Pathogenesis and disease (Chapter 32) – Human Herpesviruses

  https://www.cambridge.org/core/books/human-herpesviruses/hsv1-and-2-pathogenesis-and-disease/C6C9E1332042876CBFDA6DEEE5B5C89B

  Infection with HSV-1 generally occurs in the oropharyngeal mucosa. The trigeminal ganglion becomes colonized and harbors latent virus. However, it has been increasingly common to detect evidence of HSV-1 in the genital tract, usually the consequence of oral-genital sex. When such occurs, recurrences of HSV-1 in the genital tract are uncommon. Acquisition of HSV-2 infection is usually the consequence of transmission by genital contact. Virus replicates in the genital, perigenital or anal skin sites with seeding of the sacral ganglia.

• #25 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  Latency has been recognized biologically since the beginning of the century and has been extensively reviewed. Following entry, both HSV-1 and HSV-2 infect nerve endings and translocate by retrograde transport to the nuclei of sensory ganglia. The virus multiplies in a small number of sensory neurons, which are ultimately destroyed. In the vast majority of the infected neurons, the viral genome remains for the entire life of the individual in an episomal state. In a fraction of individuals, the virus reactivates and is moved by anterograde transport to a site at or near the portal of entry. Reactivations occur following a variety of local or systemic stimuli. […] Little is known regarding the mechanisms by which the virus establishes and maintains a latent state or is reactivated. There are in fact disagreements on the fate of neurons in which latent virus became reactivated. The relevant issues may be summarized as follows. Sensory neurons harboring virus contain nuclear transcripts arising from approximately 8.5 kbp of the sequences flanking the UL sequence. These transcripts are known as the latency associated transcripts or LATs. A shorter region is more abundantly represented in the nuclei. The RNA transcribed from this region forms two populations 2 kbp and 1.5 kbp, respectively, and represents stable introns of an unknown, and relatively unstable transcript. The abundant 2.5 and 1.5 kbp RNA play no role in the establishment or maintenance of the latent state although they may play a role in reactivation.

• #26 Herpes simplex virus – Wikipedia

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

  The late proteins form the capsid and the receptors on the surface of the virus. […] HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. […] During latent infection of a cell, HSVs express latency-associated transcript (LAT) RNA. LAT regulates the host cell genome and interferes with natural cell death mechanisms. […] A protein found in neurons may bind to herpes virus DNA and regulate latency.

• #27 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  Latency has been recognized biologically since the beginning of the century and has been extensively reviewed. Following entry, both HSV-1 and HSV-2 infect nerve endings and translocate by retrograde transport to the nuclei of sensory ganglia. The virus multiplies in a small number of sensory neurons, which are ultimately destroyed. In the vast majority of the infected neurons, the viral genome remains for the entire life of the individual in an episomal state. In a fraction of individuals, the virus reactivates and is moved by anterograde transport to a site at or near the portal of entry. Reactivations occur following a variety of local or systemic stimuli. […] Little is known regarding the mechanisms by which the virus establishes and maintains a latent state or is reactivated. There are in fact disagreements on the fate of neurons in which latent virus became reactivated. The relevant issues may be summarized as follows. Sensory neurons harboring virus contain nuclear transcripts arising from approximately 8.5 kbp of the sequences flanking the UL sequence. These transcripts are known as the latency associated transcripts or LATs. A shorter region is more abundantly represented in the nuclei. The RNA transcribed from this region forms two populations 2 kbp and 1.5 kbp, respectively, and represents stable introns of an unknown, and relatively unstable transcript. The abundant 2.5 and 1.5 kbp RNA play no role in the establishment or maintenance of the latent state although they may play a role in reactivation.

• #28 Herpes simplex virus – Wikipedia

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

  The late proteins form the capsid and the receptors on the surface of the virus. […] HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. […] During latent infection of a cell, HSVs express latency-associated transcript (LAT) RNA. LAT regulates the host cell genome and interferes with natural cell death mechanisms. […] A protein found in neurons may bind to herpes virus DNA and regulate latency.

• #29 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #30 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #31 Pathogenesis and virulence of herpes simplex virus – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34676800/

  Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes stromal keratitis, meningitis and encephalitis. […] The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. […] During primary infection, HSV infects epithelial cells in the mucosa or skin. Infection of the skin requires rupture of the keratin layer composed of dead cells. The virus replicates lytically in epithelial cells producing new infectious viral particles that reach nerve endings of peripheral neurons, where HSV establishes latency. […] Following entry in the neurite end the capsid containing pUL36 and other inner tegument proteins travel to the nucleus independently of other tegument proteins like VP16. The transport of VP16 is not efficient and it probably reaches the nucleus later than the viral DNA. This, together with other factors, leads to the deposition of histone H3 and subsequently the addition of constitutive and facultative heterochromatic marks (H3K9me3 and H3K27me3, respectively) on most viral promoters, repressing their transcription. On the contrary, the LAT locus contains facultative heterochromatin and euchromatin marks (H3K4me3 and H3K9/14acetyl), facilitating its transcription.

• #32 Herpes simplex virus – Wikipedia

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

  The late proteins form the capsid and the receptors on the surface of the virus. […] HSVs may persist in a quiescent but persistent form known as latent infection, notably in neural ganglia. […] During latent infection of a cell, HSVs express latency-associated transcript (LAT) RNA. LAT regulates the host cell genome and interferes with natural cell death mechanisms. […] A protein found in neurons may bind to herpes virus DNA and regulate latency.

• #33 Discovery reveals mechanism that turns herpes virus on and off | Cornell University College of Veterinary Medicine

  https://www.vet.cornell.edu/about-us/news/20191114/discovery-reveals-mechanism-turns-herpes-virus-and

  When the herpes virus enters a cell, the cell tries to protect itself by wrapping the viral DNA tightly around spool-like proteins called histones and condensing it into chromatin, which causes the virus to go dormant. But if the cells are unsuccessful, the chromatin is only loosely bundled, leaving the viral DNA accessible. The virus particles can then turn on their genes and replicate using the cells machinery to start a lytic infection, causing disease. […] In the new study, however, the group showed that the dynamics of the chromatin regulate whether the entire herpes virus genome is turned on, which must occur before any individual genes can be expressed. This new mechanism represents a previously overlooked way to regulate gene expression at the level of the entire viral chromosome. […] Latency and gene regulation is a big problem because we do not know nearly enough about it, said Schang. Its big black box in herpes biology.

• #34 Discovery reveals mechanism that turns herpes virus on and off | Cornell Chronicle

  https://news.cornell.edu/stories/2019/11/discovery-reveals-mechanism-turns-herpes-virus-and

  The herpes virus causes cold sores and genital sores, as well as life-threatening infections in newborns, encephalitis and corneal blindness. […] New research from Dr. Luis M. Schang and his group at the Baker Institute for Animal Health has identified a new mechanism that plays a role in controlling how the virus alternates between dormant and active stages of infection. […] In Schangs group, Mi Yao Hu and Esteban Flores Cortes discovered that the virus switches between the latent stage and the lytic stage, in which it is actively replicating, depending on how tightly its DNA is packaged into bundles called chromatin. […] Any problem that herpes causes is because of reactivation from latency, Schang said. […] When the herpes virus enters a cell, the cell tries to protect itself by wrapping the viral DNA tightly around spool-like proteins called histones and condensing it into chromatin, which causes the virus to go dormant.

• #35 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. […] The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #36 HSV-1 AND 2: Pathogenesis and disease (Chapter 32) – Human Herpesviruses

  https://www.cambridge.org/core/books/human-herpesviruses/hsv1-and-2-pathogenesis-and-disease/C6C9E1332042876CBFDA6DEEE5B5C89B

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #37 Cold sore – Wikipedia

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

  A cold sore is a type of herpes infection caused by the herpes simplex virus that affects primarily the lip. […] The cause is usually herpes simplex virus type 1 (HSV-1) and occasionally herpes simplex virus type 2 (HSV-2). […] Cold sores are the result of the virus reactivating in the body. Once HSV-1 has entered the body, it never leaves. The virus moves from the mouth to remain latent in the central nervous system. In approximately one-third of people, the virus can „wake up” or reactivate to cause disease. When reactivation occurs, the virus travels down the nerves to the skin where it may cause blisters (cold sores) around the lips or mouth area. […] Cold sore outbreaks may be influenced by stress, menstruation, sunlight, sunburn, fever, dehydration, or local skin trauma. […] The body’s immune system typically fights the virus.

• #38 Cold sore – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cold-sore/symptoms-causes/syc-20371017

  Cold sores, or fever blisters, are a common viral infection. They are tiny, fluid-filled blisters on and around the lips. These blisters are often grouped together in patches. After the blisters break, a scab forms that can last several days. Cold sores usually heal in 2 to 3 weeks without leaving a scar. […] Cold sores are caused by certain strains of the herpes simplex virus (HSV). HSV-1 usually causes cold sores. HSV-2 is often the cause of genital herpes. But either type can spread to the face or genitals through close contact, such as kissing or oral sex. Shared eating utensils, razors and towels can also spread HSV-1. […] Once you’ve had a herpes infection, the virus can hide in nerve cells in the skin and may cause another cold sore at the same place as before. A return of cold sores may be triggered by: Viral infection or fever, Hormonal changes, such as those related to a menstrual period, Stress, Fatigue, Being in the sun or wind, Changes in the immune system, Injury to the skin.

• #39 Cold sores: Foothill Dermatology Medical Center: Dermatology

  https://www.foothillderm.com/blog/cold-sores

  Cold sores are caused by the herpes simplex virus (HSV). […] Once you get the virus that causes cold sores, you have it for life. After the sores clear, the virus travels to your nerves, where it stays unless it reawakens. […] If you get cold sores, its likely that something triggers the virus to wake up. The following can be a trigger: Stress, Fatigue, Illness, such as a cold, fever, or flu, Injury, such as a cut, to the area where you have had cold sores, Dental work, Cosmetic surgery or laser treatment, Strong sunlight, Certain foods, Hormonal changes, such as getting your period. […] Cold sores cannot be cured. Some people get the virus and have just one outbreak. Others continue to get cold sores. […] Taking this medicine at the start of a cold-sore outbreak can shorten the amount of time you have cold sores. Some people who get cold sores frequently take this medicine every day. Taken daily, it can help prevent outbreaks of cold sores.

• #40 Discovery shows how herpes simplex virus reactivates in neurons to trigger disease | ScienceDaily

  https://www.sciencedaily.com/releases/2015/12/151209143105.htm

  When we get cold sores, the reason is likely related to stress. For the first time, researchers at the University of North Carolina School of Medicine discovered a cellular mechanism that allows the herpes simplex virus to reactivate. They also found how brain cells are duped into allowing bits of virus to escape the very repressive environment in neurons and cause disease. […] „We’ve known that stress triggers viral reactivation. What we’ve now found is how stress at the cellular level allows for viral reactivation.” […] „We’re excited about the possibility that this stress-activation pathway exists in humans,” said Mohanish Deshmukh, the paper’s senior author and professor of cell biology and physiology at UNC. „All of the elements of these pathways are found in human neurons. And we know that stress reactivates herpes simplex virus in humans.”

• #41 Discovery shows how herpes simplex virus reactivates in neurons to trigger disease | ScienceDaily

  https://www.sciencedaily.com/releases/2015/12/151209143105.htm

  „When our bodies are stressed, we release high levels of corticosteroids,” Cliffe said. „So, using it in this experiment was a good way to mimic what could happen in the body.” […] „We then used a chemical inhibitor to block the JNK pathway to see if that stopped viral reactivation,” said Deshmukh, who is a member of the UNC Neuroscience Center. „And it had a spectacular effect. When we inhibited JNK, the virus was no longer able to reactivate.” […] „Most scientists who study the genome would be surprised with that finding,” Deshmukh said. „The methyl marks — these epigenetic modifications — must be taken off before DNA can be opened. And that’s true. But we’ve found a great case where we see gene expression even in the presence of methyl marks.” […] „You could say that the methyl marks act as brakes to refuse gene expression,” Deshmukh said. „And this phosphorylation releases the brakes just enough so that a little bit of viral gene expression can occur. This is called a methyl/phospho switch.”

• #42 Discovery reveals mechanism that turns herpes virus on and off | Cornell University College of Veterinary Medicine

  https://www.vet.cornell.edu/about-us/news/20191114/discovery-reveals-mechanism-turns-herpes-virus-and

  Discovery reveals mechanism that turns herpes virus on and off […] New research from Dr. Luis Schang and his group at the Baker Institute for Animal Health has identified a mechanism that plays a role in controlling how the virus alternates between dormant and active stages of infection. […] In Schangs group, Mi Yao Hu and Esteban Flores Cortes discovered that the virus switches between the latent stage and the lytic stage, in which it is actively replicating, depending on how tightly its DNA is packaged into bundles called chromatin. […] Any problem that herpes causes is because of reactivation from latency, Schang said. Thats the reason why antivirals cannot cure the infection and why so far its been impossible to develop a vaccine. Latency and reactivation are a major focus for herpes virus research.

• #43 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-ups – Department of Microbiology, Immunology, and Cancer Biology

  https://med.virginia.edu/mic/2025/02/28/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus, said Cliffe of UVAs Department of Microbiology, Immunology and Cancer Biology. […] The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said.

• #44 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] The discovery from UVAs Anna Cliffe, PhD, and colleagues seems to defy common sense. She and her team found that the slumbering herpes virus will make a protein to trigger the bodys immune response as part of its escape from dormancy. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus. […] This is important because it gives us new ways to potentially prevent the virus from waking up and activating immune responses in the nervous system that could have negative consequences in the long term.

• #45 Cold sore discovery identifies unknown trigger for those annoying flare-ups

  https://medicalxpress.com/news/2025-02-cold-sore-discovery-unknown-trigger.html

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] The discovery from UVA’s Anna Cliffe, Ph.D., and colleagues seems to defy common sense. She and her team found that the slumbering herpes virus will make a protein to trigger the body’s immune response as part of its escape from dormancy. […] „Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus,” said Cliffe of UVA’s Department of Microbiology, Immunology and Cancer Biology. […] The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection.

• #46 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-ups – Department of Microbiology, Immunology, and Cancer Biology

  https://med.virginia.edu/mic/2025/02/28/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus, said Cliffe of UVAs Department of Microbiology, Immunology and Cancer Biology. […] The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said.

• #47 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] The discovery from UVAs Anna Cliffe, PhD, and colleagues seems to defy common sense. She and her team found that the slumbering herpes virus will make a protein to trigger the bodys immune response as part of its escape from dormancy. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus. […] This is important because it gives us new ways to potentially prevent the virus from waking up and activating immune responses in the nervous system that could have negative consequences in the long term.

• #48 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] Detection of a pathogen alone may be sufficient to trigger the herpes virus to begin replicating, the scientists believe, even in instances of abortive infections when the immune system contains the new pathogen before it can replicate. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said. […] With the new understanding of how herpes flares can be triggered, scientists may be able to target the protein to prevent them, the researchers say. […] Currently, there are no therapies that can prevent the virus from waking up from dormancy, and this stage was thought to only use host proteins. Developing therapies that specifically act on a viral protein is an attractive approach that will likely have fewer side effects than targeting a host protein.

• #49 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #50 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #51 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #52

  https://step2.medbullets.com/dermatology/120052/herpes-simplex

  caused by two major strains of the Herpes simplex virus (HSV) […] Transmission occurs from direct contact with active lesions […] Virus resides in the dorsal root ganglia of local nerves until reactivation […] mechanism for recurrence is not well-understood […] immunosuppression plays a role […] Intrahost viral spread occurs via epidermal cells […] subsequent abnormal cell division creates multinucleated „giant cells”

• #53 What Herpes Looks Like: Pictures, Prevention, Treatment

  https://www.verywellhealth.com/herpes-simplex-pictures-4020363

  Both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) stay with you forever, once you’re infected. The inactive virus will embed itself in nerve cells near the spinal cord. […] When herpes reactivates, the virus will travel up the string of nerves to the surface of the skin where it will cause an outbreak of tiny blisters called vesicles. The vesicles will then erupt, causing painful open ulcers commonly referred to as herpes sores. […] The ulcerative stage begins when the blisters break open to form skin ulcers. […] Severe cases like this tend to occur during a first outbreak (called primary herpes). Thereafter, the body will have produced immune proteins, called antibodies, that are not able to neutralize the virus but can help control the infection. […] Cold sores (also called fever blisters, oral herpes, or orolabial herpes) are more often caused by HSV-1 than HSV-2. Cold sores progress in much the same way as genital herpes. HSV-1 can also affect the tongue, gums, or face.

• #54 Pathogen Safety Data Sheets: Infectious Substances – Herpes simplex virus – Canada.ca

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

  Herpes labialis/cold sores: Caused mainly by HSV-1, there have been reported cases caused by HSV-2. Primary infections with HSV-1 are acquired usually in childhood and may be asymptomatic or subclinical. Symptomatic primary infections present mainly as gingivostomatitis, with fever, sore throat, fetor oris, anorexia, cervical adenopathy, and mucosal edema and vesicular and ulcerative painful lesions involving the buccal mucosa, tongue, gums, and pharynx. Ulcers heal without scarring within 2-3 weeks. Recurrent infections have generally milder symptoms and clinical course. Recurrent lesions due to HSV-1 occur mainly on a specific area of the lip (vermillion border of the lip), and are called „cold sores” or „fever blisters.” The lesions heal in approximately 8-10 days. […] Encephalitis: Serious infections of the CNS, affecting both children and adolescents. It may occur due to primary or latent infection with HSV-1 virus. HSV encephalitis affects one temporal lobe, leading to focal neurologic signs and edema. The disease can be fatal (mortality rate of 70%), if left untreated.

• #55 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #56 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #57 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #58 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The exact mechanism behind this is not clear, but it is known that some conditions seem to trigger recurrences, including: Fever, cold, or the flu; UV rays (sun exposure or a sunburn); Emotional or physical stress (such as an illness or surgery); Weakening of the immune system; Trauma to the involved area such as dental work. […] Cold sores are caused by the herpes simplex virus (HSV). […] In general, HSV-1, also known as herpes labialis or oral herpes, causes infections above the waist, most commonly as „cold sores.” […] However, both types of HSV are capable of infecting the skin at any location on the body. […] The process generates an antibody response, causing the immune system to produce antibodies against the herpes virus. This antibody response helps reduce recurrences and keep them mild.

• #59 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The histopathologic characteristics of a primary or recurrent HSV reflect viral-mediated cellular death and associated inflammatory response. Viral infection induces ballooning of cells with condensed chromatic within the nuclei of cells, followed by nuclear degeneration, generally within parabasal and intermediate cells of the epithelium. Cells lose intact plasma membranes and form multinucleated giant cells. With cell lysis, a clear (referred to as vesicular) fluid containing large quantities of virus appears between the epidermis and dermal layer. […] The pathogenesis of HSV infections is influenced by both specific and non-specific host defense mechanisms. With the appearance of non-specific inflammatory changes, paralleling a peak in viral replication, specific host responses can be quantitated but vary from one animal system to the next. In the mouse, delayed-type hypersensitivity responses are identified within 46 days after disease onset, followed by a cytotoxic T-cell response and by the appearance of both IgM- and IgG-specific antibodies. Host responses in humans are delayed, developing approximately 710 days later.

• #60 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The exact mechanism behind this is not clear, but it is known that some conditions seem to trigger recurrences, including: Fever, cold, or the flu; UV rays (sun exposure or a sunburn); Emotional or physical stress (such as an illness or surgery); Weakening of the immune system; Trauma to the involved area such as dental work. […] Cold sores are caused by the herpes simplex virus (HSV). […] In general, HSV-1, also known as herpes labialis or oral herpes, causes infections above the waist, most commonly as „cold sores.” […] However, both types of HSV are capable of infecting the skin at any location on the body. […] The process generates an antibody response, causing the immune system to produce antibodies against the herpes virus. This antibody response helps reduce recurrences and keep them mild.

• #61 Herpes Simplex: Background, Microbiology, Pathophysiology

  https://emedicine.medscape.com/article/218580-overview

  Cellular immunity is an important defense against herpes simplex. Dissemination of herpes simplex infection can occur in people with impaired T-cell immunity, such as in organ transplant recipients and in individuals with AIDS. Herpes simplex infection can also complicate burn wounds or damaged skin such as in atopic dermatitis or other allergic dermatoses. […] HSV is transmitted by close personal contact, and infection occurs via inoculation of virus into susceptible mucosal surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks in the skin. The virus is readily inactivated at room temperature and by drying; hence, aerosol and fomitic spread are rare.

• #62 Herpes simplex virus – Wikipedia

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

  HSV-1 and -2 persist in the body by hiding from the immune system in the cell bodies of neurons, particularly in sensory ganglia. […] After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron’s axon to the skin, where virus replication and shedding occur and may cause new sores. […] HSV evades the immune system through interference with MHC class I antigen presentation on the cell surface, by blocking the transporter associated with antigen processing (TAP) induced by the secretion of ICP-47 by HSV. […] Following the infection of a cell, a cascade of herpes virus proteins, called immediate-early, early, and late, is produced. […] The early proteins transcribed are used in the regulation of genetic replication of the virus.

• #63 The Rockefeller University » Study reveals how herpes virus tricks the immune system

  https://www.rockefeller.edu/news/10718-study-reveals-how-herpes-virus-tricks-the-immune-system/

  With over half the U.S. population infected, most people are familiar with the pesky cold sore outbreaks caused by the herpes virus. The virus outsmarts the immune system by interfering with the process that normally allows immune cells to recognize and destroy foreign invaders. […] A team of structural biologists in Jue Chens Laboratory of Membrane Biology and Biophysics have captured atomic images of the virus in action, revealing how it inserts itself into another protein to cause a traffic jam in an important immune system pathway. […] This work illustrates a striking example of how a persistent virus evades the immune system, says Chen. Once this virus enters the body, it never leaves. Our findings provide a mechanistic explanation for how its able to escape detection by immune cells.

• #64 The Rockefeller University » Study reveals how herpes virus tricks the immune system

  https://www.rockefeller.edu/news/10718-study-reveals-how-herpes-virus-tricks-the-immune-system/

  We knew that TAP was involved in our inability to have an effective immune response to this virus, but no one really knew what TAP looks like, or how it works, says Chen. Our findings show exactly how this viral protein jams TAP, which has two effects. One, it precludes the regular protein from binding. Two, it makes the transporter stuck in this conformation. […] However, understanding the various ways viruses block transporters could be harnessed for treating other diseases. TAP is a member of a family of transporters that are found across human cells, a number of which pump molecules like nutrients and drugs across membranes to various cellular compartments. […] We havent been able to figure out how to block these transporters ourselves, says Chen, so we are learning how its done from viruses, which we hope will teach us some strategies for inhibition.

• #65 The Rockefeller University » Study reveals how herpes virus tricks the immune system

  https://www.rockefeller.edu/news/10718-study-reveals-how-herpes-virus-tricks-the-immune-system/

  With over half the U.S. population infected, most people are familiar with the pesky cold sore outbreaks caused by the herpes virus. The virus outsmarts the immune system by interfering with the process that normally allows immune cells to recognize and destroy foreign invaders. […] A team of structural biologists in Jue Chens Laboratory of Membrane Biology and Biophysics have captured atomic images of the virus in action, revealing how it inserts itself into another protein to cause a traffic jam in an important immune system pathway. […] This work illustrates a striking example of how a persistent virus evades the immune system, says Chen. Once this virus enters the body, it never leaves. Our findings provide a mechanistic explanation for how its able to escape detection by immune cells.

• #66 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. […] Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study. […] Viral strain, environmental factors and genetics are believed to account for the observed differences in disease expression among those infected with HSV1. […] Our group previously identified a region of chromosome 21 that is significantly linked to Herpes simplex labialis disease. […] The association of individual SNP genotypes with Herpes simplex labialis frequency was evaluated using linkage analysis and transmission disequilibrium testing.

• #67 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. […] Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study. […] Viral strain, environmental factors and genetics are believed to account for the observed differences in disease expression among those infected with HSV1. […] Our group previously identified a region of chromosome 21 that is significantly linked to Herpes simplex labialis disease. […] The association of individual SNP genotypes with Herpes simplex labialis frequency was evaluated using linkage analysis and transmission disequilibrium testing.

• #68 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. […] Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study. […] Viral strain, environmental factors and genetics are believed to account for the observed differences in disease expression among those infected with HSV1. […] Our group previously identified a region of chromosome 21 that is significantly linked to Herpes simplex labialis disease. […] The association of individual SNP genotypes with Herpes simplex labialis frequency was evaluated using linkage analysis and transmission disequilibrium testing.

• #69 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  The previous study implicating CSSG-1 in herpes disease expression was performed in a familial sample. […] Therefore, a case-control study in an entirely new, unrelated human population was performed to investigate the proposed effects of the gene CSSG-1 (c21orf91) on the susceptibility to cold sores. […] This study evaluated the effects of CSSG-1, a putative herpes susceptibility gene, on the expression of cold sores in a larger, unrelated human population. […] One or more CSSG-1 haplotypes significantly affected the reported number of annual cold sore outbreaks, the number of reported lifetime cold sores and perceived cold sore severity. […] The CSSG-1 haplotypes generally did not affect HSV1 serostatus (i.e., infection with HSV1) or the EI (quantity and affinity of anti-HSV1 antibodies).

• #70 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  The age, sex and ethnicity-adjusted data here suggested significant protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2 and H4 haplotypes tended to be subject to more frequent and more severe episodes. […] The relatively protective H3 and H5/H6 haplotypes carry SNPs in the 3 UTR (3 untranslated region or 3 Tag SNP) of the gene. […] Our data do not allow us to predict if these effects are associated with increased or decreased CSSG-1 protein production. […] In conclusion, the present study confirms the activity of a previously unknown herpes susceptibility gene, CSSG-1, in a new population of unrelated humans. […] The mechanism of CSSG-1 action is unknown.

• #71 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  The age, sex and ethnicity-adjusted data here suggested significant protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2 and H4 haplotypes tended to be subject to more frequent and more severe episodes. […] The relatively protective H3 and H5/H6 haplotypes carry SNPs in the 3 UTR (3 untranslated region or 3 Tag SNP) of the gene. […] Our data do not allow us to predict if these effects are associated with increased or decreased CSSG-1 protein production. […] In conclusion, the present study confirms the activity of a previously unknown herpes susceptibility gene, CSSG-1, in a new population of unrelated humans. […] The mechanism of CSSG-1 action is unknown.

• #72 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  The age, sex and ethnicity-adjusted data here suggested significant protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2 and H4 haplotypes tended to be subject to more frequent and more severe episodes. […] The relatively protective H3 and H5/H6 haplotypes carry SNPs in the 3 UTR (3 untranslated region or 3 Tag SNP) of the gene. […] Our data do not allow us to predict if these effects are associated with increased or decreased CSSG-1 protein production. […] In conclusion, the present study confirms the activity of a previously unknown herpes susceptibility gene, CSSG-1, in a new population of unrelated humans. […] The mechanism of CSSG-1 action is unknown.

• #73 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  The age, sex and ethnicity-adjusted data here suggested significant protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2 and H4 haplotypes tended to be subject to more frequent and more severe episodes. […] The relatively protective H3 and H5/H6 haplotypes carry SNPs in the 3 UTR (3 untranslated region or 3 Tag SNP) of the gene. […] Our data do not allow us to predict if these effects are associated with increased or decreased CSSG-1 protein production. […] In conclusion, the present study confirms the activity of a previously unknown herpes susceptibility gene, CSSG-1, in a new population of unrelated humans. […] The mechanism of CSSG-1 action is unknown.

• #74 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The current FDA-approved oral antiviral drugs used in the treatment of herpes simplex virus in adults are acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir). These oral medications have been shown to decrease the duration of the outbreak, especially when started during the prodrome before the rash appears. […] Currently, there is no cure or vaccine for the herpes simplex virus. Avoiding risk factors, such as sunburn and stress, can help prevent additional outbreaks. […] A more serious complication is infection of the eye, or ocular herpes (herpetic keratitis). […] Rarely, herpes simplex may infect the brain, causing encephalitis. This infection requires hospitalization and intravenous antiviral medications. […] In immunocompromised people, such as those with HIV infection or those receiving chemotherapy, severe outbreaks of herpes may occur.

• #75 Treatment and prevention of herpes simplex virus type 1 in immunocompetent adolescents and adults – UpToDate

  https://www.uptodate.com/contents/treatment-and-prevention-of-herpes-simplex-virus-type-1-in-immunocompetent-adolescents-and-adults

  Herpes simplex virus type 1 (HSV-1) is a cause of recurrent vesiculoulcerative lesions of the oral or genital mucosa. It can also cause infection in the eye, skin, central nervous system, and/or visceral organs. […] The management of HSV-1 infection in the immunocompetent host depends upon a variety of considerations, including: Whether the patient has primary HSV-1 infection or reactivation disease, the severity of symptoms, the site of infection (eg, mucosal versus disseminated disease), the frequency of recurrences. Antiviral agents for HSV infection include acyclovir, valacyclovir, and famciclovir. Metabolites of these nucleoside derivatives interfere with the synthesis of viral DNA by inhibiting viral DNA polymerase. […] Oral HSV-1 recurrences occur when the virus reactivates from the trigeminal sensory ganglion, where it persists in a latent state. Symptomatic reactivation leads to oral herpes („cold sores”), which occur along the vermillion border of the lips.

• #76 Cold sores: Diagnosis and treatment

  https://www.aad.org/public/diseases/a-z/cold-sores-treatment

  Cold sores are caused by a virus, so antiviral medications are used to treat them. Your dermatologist may include one of the following antiviral medications in your treatment plan: […] Your dermatologist may also dab a swab, called a culture swab, onto a cold sore to find out if it contains the herpes simplex virus (HSV). This is the virus that causes cold sores. […] Treating a cold sore before it appears (or when you first see it) can reduce your discomfort and speed up healing. […] The sun triggers cold sores for some people. Wearing lip balm year-round that has SPF 30 or higher and broad-spectrum protection may help prevent new cold sores. […] Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007;57(5):737-63. […] Gopinath D, Koe KH, et al. A comprehensive overview of epidemiology, pathogenesis, and the management of herpes labialis. Viruses. 2023 Jan 13;15(1):225.

• #77 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The current FDA-approved oral antiviral drugs used in the treatment of herpes simplex virus in adults are acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir). These oral medications have been shown to decrease the duration of the outbreak, especially when started during the prodrome before the rash appears. […] Currently, there is no cure or vaccine for the herpes simplex virus. Avoiding risk factors, such as sunburn and stress, can help prevent additional outbreaks. […] A more serious complication is infection of the eye, or ocular herpes (herpetic keratitis). […] Rarely, herpes simplex may infect the brain, causing encephalitis. This infection requires hospitalization and intravenous antiviral medications. […] In immunocompromised people, such as those with HIV infection or those receiving chemotherapy, severe outbreaks of herpes may occur.

• #78 What Herpes Looks Like: Pictures, Prevention, Treatment

  https://www.verywellhealth.com/herpes-simplex-pictures-4020363

  HSV-2 is often thought of as genital herpes but HSV-1 can also be passed to the genitals or anus via oral sex. HSV-1 that causes a genital herpes outbreak is less virulent and less likely to recur. […] Both HSV-1 and HSV-2 are treated with antiviral drugs. They are most effective when started within 48 to 72 hours of the first signs of an outbreak. They do not cure herpes but may reduce the severity and duration of an outbreak.

• #79 Valacyclovir (Valtrex): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD

  https://www.webmd.com/drugs/2/drug-6279/valacyclovir-oral/details

  Valacyclovir is an antiviral medicine that stops the growth of herpes viruses and reduces the amount of outbreaks you have. Valacyclovir does not remove the viruses from your body. […] Valacyclovir is not a cure for cold sores, genital herpes, chickenpox, or shingles.

• #80 Aciclovir, acyclovir

  https://dermnetnz.org/topics/aciclovir

  Aciclovir is a synthetic compound with a similar molecular structure to purine nucleoside. It has been shown to stop the growth of herpes simplex virus (HSV), Varicella zoster virus (VZV) (the cause of chickenpox and shingles), Epstein-Barr virus (EBV, the cause of infectious mononucleosis), and to a lesser extent cytomegalovirus (CMV). […] To become effective, aciclovir must first be changed to aciclovir monophosphate by an enzyme that is only found in viruses, called thymidine kinase (TK). It is then converted to its active triphosphate form by human enzymes found inside the cells. […] Aciclovir triphosphate (AT) is the active form of the drug. It reduces the production of viral DNA by competing with a natural compound, deoxyguanosine triphosphate, for the viral DNA polymerase enzyme. Incorporation of AT into the viral DNA completely prevents the synthesis of new DNA. […] Viral DNA polymerase binds 1030 times more strongly to AT than the cellular DNA polymerase. This means aciclovir is not toxic.

• #81 What is the mechanism of Docosanol?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-docosanol

  Docosanol, also known by its brand name Abreva, is an over-the-counter medication widely used to treat cold sores caused by the herpes simplex virus (HSV). […] The primary mechanism of docosanol is thus to inhibit the fusion between the viral envelope and the host cell membrane. By preventing this critical step, docosanol effectively blocks the entry of the virus into the host cells. This action significantly reduces the ability of the virus to replicate and spread, which in turn helps to limit the severity and duration of cold sore outbreaks. […] In summary, the mechanism of docosanol involves its integration into the lipid envelope of the herpes simplex virus, where it impairs the virus’s ability to fuse with and enter host cells. By blocking this initial step of viral infection, docosanol helps to limit the replication and spread of the virus, thereby reducing the severity and duration of cold sore episodes.

• #82 The Mechanism of Action Behind Abreva’s Effectiveness | CareCard

  https://carecard.com/blog/the-mechanism-of-action-behind-abrevas-effectiveness

  Abreva, with docosanol as its active ingredient, is used to treat herpes simplex virus (HSV) infections, specifically cold sores or fever blisters. Cold sores are painful and often recurrent, making effective treatment essential for those affected. […] Docosanol inhibits the fusion between the herpes simplex virus and the host cell membrane. This prevents the virus from entering the host cells, thereby stopping the infection from spreading. Specifically, docosanol integrates into the host cell’s plasma membrane, creating a physical barrier that blocks the viral entry. […] By blocking the virus’s entry into host cells, docosanol also prevents the virus’s replication. Without entry into the host cell, the virus cannot use the cellular machinery to replicate, effectively reducing the viral load and the severity of symptoms.

• #83 The Mechanism of Action Behind Abreva’s Effectiveness | CareCard

  https://carecard.com/blog/the-mechanism-of-action-behind-abrevas-effectiveness

  Abreva, with docosanol as its active ingredient, is used to treat herpes simplex virus (HSV) infections, specifically cold sores or fever blisters. Cold sores are painful and often recurrent, making effective treatment essential for those affected. […] Docosanol inhibits the fusion between the herpes simplex virus and the host cell membrane. This prevents the virus from entering the host cells, thereby stopping the infection from spreading. Specifically, docosanol integrates into the host cell’s plasma membrane, creating a physical barrier that blocks the viral entry. […] By blocking the virus’s entry into host cells, docosanol also prevents the virus’s replication. Without entry into the host cell, the virus cannot use the cellular machinery to replicate, effectively reducing the viral load and the severity of symptoms.

• #84 Cold sore treatment: 4 methods to improve healing | Perio Implant Advisory

  https://www.perioimplantadvisory.com/clinical-tips/article/14303292/cold-sore-treatment-4-methods-to-improve-healing

  Cold sores, or herpes labialis, are also known as sun blisters a common viral infection of the lips or mouth area caused by the herpes simplex virus (HSV). […] Cold sores do not have a cure, and treatment usually involves antiviral drugs such as acyclovir, penciclovir, and valacyclovir in cream or tablet form. These treatments work to slow or inhibit viral replication via the herpesvirus DNA polymerase, but do not completely eliminate the virus or its recurrence. […] The most important complex chemical compound that renders propolis an antiviral agent is phenolic acid, which can negatively affect HSV-1 and HSV-2 viral replication in host cells. […] Low-level laser therapy (LLLT) is a type of medical treatment that uses lasers or light-emitting diodes to stimulate cells in the body and promote healing. This treatment can prevent or shorten herpes labialis outbreaks by delivering low levels of laser energy to the target area usually in the range of 248 J/cm2. […] RILT modulates reactive oxygen species leading to repair of virally induced DNA damage. […] More research and standardized protocols are needed in this area to truly recognize the benefits of RILT in the treatment of cold sores.

• #85 Autophagy Stimulation Abrogates Herpes simplex Virus-1 Infection | Scientific Reports

  https://www.nature.com/articles/srep09730

  Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. A major virulence mechanism of HSV-1 is the control of autophagy, an innate immune defense strategy that could otherwise degrade viral particles. This study establishes the importance of autophagy for regulating HSV-1 infection and provides a proof-of-principle evidence for a novel antiviral mechanism. […] HSV-1 is a double-stranded DNA virus that controls host’s autophagic responses through binding of the viral protein ICP34.5 to the host protein beclin1, leading to inhibition of autophagy. Since control of autophagy is a robust virulence mechanism of the virus, we reasoned that enabling autophagy activation in infection may suppress the infection and thus provide an unprecedented antiviral therapeutic tool.

• #86 Treating cold sores in two days and canker sores through glutathione antioxidation | Perio Implant Advisory

  https://www.perioimplantadvisory.com/periodontics/oral-pathology/article/55087903/treating-cold-sores-in-two-days-and-canker-sores-through-glutathione-antioxidation

  Cold sores, caused by the herpes simplex virus (HSV), manifest as painful blisters on the lips and around the mouth. […] Cold sores are primarily caused by HSV-1, a virus that induces oxidative stress upon infection and generates ROS, which can damage cellular components and exacerbate the inflammatory response. […] By enhancing the antioxidative capacity of cells, glutathione can mitigate this damage and inhibit viral replication. […] A study by Ozbalci et al. (2014) demonstrated that increasing intracellular GSH levels in HSV-1 infected cells reduced the production of viral particles. […] This suggests that glutathione’s antioxidative properties can directly interfere with the viral life cycle, potentially reducing the severity and duration of cold sore outbreaks. […] Additionally, glutathione can modulate the immune response, which is crucial for controlling HSV-1 infections.

• #87 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] Detection of a pathogen alone may be sufficient to trigger the herpes virus to begin replicating, the scientists believe, even in instances of abortive infections when the immune system contains the new pathogen before it can replicate. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said. […] With the new understanding of how herpes flares can be triggered, scientists may be able to target the protein to prevent them, the researchers say. […] Currently, there are no therapies that can prevent the virus from waking up from dormancy, and this stage was thought to only use host proteins. Developing therapies that specifically act on a viral protein is an attractive approach that will likely have fewer side effects than targeting a host protein.

• #88 Cold sore discovery identifies unknown trigger for those annoying flare-ups

  https://medicalxpress.com/news/2025-02-cold-sore-discovery-unknown-trigger.html

  „We were surprised to find that HSV-1 doesn’t just passively wait for the right conditions to reactivate—it actively senses danger and takes control of the process,” researcher Patryk Krakowiak said. […] With the new understanding of how herpes flares can be triggered, scientists may be able to target the protein to prevent them, the researchers say. […] „Currently, there are no therapies that can prevent the virus from waking up from dormancy, and this stage was thought to only use host proteins. Developing therapies that specifically act on a viral protein is an attractive approach that will likely have fewer side effects than targeting a host protein.”

• #89 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] Detection of a pathogen alone may be sufficient to trigger the herpes virus to begin replicating, the scientists believe, even in instances of abortive infections when the immune system contains the new pathogen before it can replicate. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said. […] With the new understanding of how herpes flares can be triggered, scientists may be able to target the protein to prevent them, the researchers say. […] Currently, there are no therapies that can prevent the virus from waking up from dormancy, and this stage was thought to only use host proteins. Developing therapies that specifically act on a viral protein is an attractive approach that will likely have fewer side effects than targeting a host protein.

• #90 New Target for Antiviral Herpes Therapies | 2024 | News and Press | News | Leibniz Institute of Virology

  https://www.leibniz-liv.de/en/news/news-and-press/new-target-for-antiviral-herpes-therapies

  New Target for Antiviral Herpes Therapies […] Key Mechanism of Herpesvirus Egress Uncovered […] The new study focuses on Herpes simplex virus 1 – the causative agent of oral cold sores – and Pseudorabies virus (PrV), a model virus for human herpes infections. The researchers identified various structures of the herpesviral nuclear egress complex (NEC) protein coat located on the inner nuclear membrane. These structures are critical for the release of capsids into the cytosol, where they can acquire the envelope before leaving the cell. […] The findings indicate a remarkable structural flexibility of the NEC, suggesting that the mechanism is not rigid but adaptive. […] Overall, the new insights from this study offer promising perspectives for combating herpesvirus infections. The nanoscale structural insights determined by the researchers lay the foundation for understanding the complex nuclear egress mechanism common to all herpesviruses.

• #91 New Target for Antiviral Herpes Therapies | 2024 | News and Press | News | Leibniz Institute of Virology

  https://www.leibniz-liv.de/en/news/news-and-press/new-target-for-antiviral-herpes-therapies

  New Target for Antiviral Herpes Therapies […] Key Mechanism of Herpesvirus Egress Uncovered […] The new study focuses on Herpes simplex virus 1 – the causative agent of oral cold sores – and Pseudorabies virus (PrV), a model virus for human herpes infections. The researchers identified various structures of the herpesviral nuclear egress complex (NEC) protein coat located on the inner nuclear membrane. These structures are critical for the release of capsids into the cytosol, where they can acquire the envelope before leaving the cell. […] The findings indicate a remarkable structural flexibility of the NEC, suggesting that the mechanism is not rigid but adaptive. […] Overall, the new insights from this study offer promising perspectives for combating herpesvirus infections. The nanoscale structural insights determined by the researchers lay the foundation for understanding the complex nuclear egress mechanism common to all herpesviruses.

• #92

  https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus

  Herpes simplex virus lives inside of nerve cells and alternates between being inactive and active. Certain triggers can reactivate the virus including: […] HSV-2 infection increases the risk of acquiring HIV infection by approximately three-fold. Additionally, people with both HIV and HSV-2 infection are more likely to spread HIV to others. HSV-2 infection is among the most common infections in people living with HIV. […] In immunocompromised people, including those with advanced HIV infection, herpes can have more severe symptoms and more frequent recurrences. Rare complications of HSV-2 include meningoencephalitis (brain infection) and disseminated infection. Rarely, HSV-1 infection can lead to more severe complications such as encephalitis (brain infection) or keratitis (eye infection).

• #93 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The current FDA-approved oral antiviral drugs used in the treatment of herpes simplex virus in adults are acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir). These oral medications have been shown to decrease the duration of the outbreak, especially when started during the prodrome before the rash appears. […] Currently, there is no cure or vaccine for the herpes simplex virus. Avoiding risk factors, such as sunburn and stress, can help prevent additional outbreaks. […] A more serious complication is infection of the eye, or ocular herpes (herpetic keratitis). […] Rarely, herpes simplex may infect the brain, causing encephalitis. This infection requires hospitalization and intravenous antiviral medications. […] In immunocompromised people, such as those with HIV infection or those receiving chemotherapy, severe outbreaks of herpes may occur.

• #94 Herpes Simplex Encephalitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1165183-overview

  Herpes simplex encephalitis (HSE) is an acute or subacute illness that causes both general and focal signs of cerebral dysfunction. Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve and indirect immune-mediated processes inducing neuroinflammation. […] The exact mechanism of cellular damage is unclear, but it may involve both direct virus-mediated and indirect immune-mediated processes. The ability of HSV-1 to induce apoptosis (programmed cell death, or cellular suicide) in neuronal cells, a property not shared by HSV-2, might explain why the former causes virtually all cases of herpes simplex encephalitis in immunocompetent older children and adults. […] Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve. Factors that precipitate HSE are unknown.

• #95 Herpes Simplex Encephalitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1165183-overview

  Herpes simplex encephalitis (HSE) is an acute or subacute illness that causes both general and focal signs of cerebral dysfunction. Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve and indirect immune-mediated processes inducing neuroinflammation. […] The exact mechanism of cellular damage is unclear, but it may involve both direct virus-mediated and indirect immune-mediated processes. The ability of HSV-1 to induce apoptosis (programmed cell death, or cellular suicide) in neuronal cells, a property not shared by HSV-2, might explain why the former causes virtually all cases of herpes simplex encephalitis in immunocompetent older children and adults. […] Brain infection is thought to occur by means of direct neuronal transmission of the virus from a peripheral site to the brain via the trigeminal or olfactory nerve. Factors that precipitate HSE are unknown.

• #96

  https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus

  Herpes simplex virus lives inside of nerve cells and alternates between being inactive and active. Certain triggers can reactivate the virus including: […] HSV-2 infection increases the risk of acquiring HIV infection by approximately three-fold. Additionally, people with both HIV and HSV-2 infection are more likely to spread HIV to others. HSV-2 infection is among the most common infections in people living with HIV. […] In immunocompromised people, including those with advanced HIV infection, herpes can have more severe symptoms and more frequent recurrences. Rare complications of HSV-2 include meningoencephalitis (brain infection) and disseminated infection. Rarely, HSV-1 infection can lead to more severe complications such as encephalitis (brain infection) or keratitis (eye infection).

• #97

  https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus

  Herpes simplex virus lives inside of nerve cells and alternates between being inactive and active. Certain triggers can reactivate the virus including: […] HSV-2 infection increases the risk of acquiring HIV infection by approximately three-fold. Additionally, people with both HIV and HSV-2 infection are more likely to spread HIV to others. HSV-2 infection is among the most common infections in people living with HIV. […] In immunocompromised people, including those with advanced HIV infection, herpes can have more severe symptoms and more frequent recurrences. Rare complications of HSV-2 include meningoencephalitis (brain infection) and disseminated infection. Rarely, HSV-1 infection can lead to more severe complications such as encephalitis (brain infection) or keratitis (eye infection).

• #98 Cold Sores (Oral Herpes): Causes, Oral Symptoms, & Treatment

  https://www.medicinenet.com/herpes_simplex_infections_non-genital/article.htm

  The current FDA-approved oral antiviral drugs used in the treatment of herpes simplex virus in adults are acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir). These oral medications have been shown to decrease the duration of the outbreak, especially when started during the prodrome before the rash appears. […] Currently, there is no cure or vaccine for the herpes simplex virus. Avoiding risk factors, such as sunburn and stress, can help prevent additional outbreaks. […] A more serious complication is infection of the eye, or ocular herpes (herpetic keratitis). […] Rarely, herpes simplex may infect the brain, causing encephalitis. This infection requires hospitalization and intravenous antiviral medications. […] In immunocompromised people, such as those with HIV infection or those receiving chemotherapy, severe outbreaks of herpes may occur.

• #99 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. […] The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #100 HSV-1 AND 2: Pathogenesis and disease (Chapter 32) – Human Herpesviruses

  https://www.cambridge.org/core/books/human-herpesviruses/hsv1-and-2-pathogenesis-and-disease/C6C9E1332042876CBFDA6DEEE5B5C89B

  The transmission of herpes simplex virus (HSV) infection is dependent upon intimate, personal contact of a susceptible seronegative individual with someone excreting HSV. Virus must come in contact with mucosal surfaces or abraded skin for infection to be initiated. With viral replication at the site of primary infection, either an intact virion or, more simply, the capsid is transported retrograde by neurons to the dorsal root ganglia where, after another round of viral replication, latency is established. The more severe the primary infection, as reflected by the size, number, and extent of lesions, the more likely it is that recurrences will ensue. Although replication sometimes leads to disease and, infrequently, results in life-threatening infection (e.g., encephalitis), the host-virus interaction leading to latency predominates. After latency is established, a proper stimulus causes reactivation; virus becomes evident at mucocutaneous sites, appearing as skin vesicles or mucosal ulcers.

• #101 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-ups – Department of Microbiology, Immunology, and Cancer Biology

  https://med.virginia.edu/mic/2025/02/28/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus, said Cliffe of UVAs Department of Microbiology, Immunology and Cancer Biology. […] The researchers found that while the virus can make a protein called UL12.5 to reactivate, the protein was not needed in the presence of another infection. […] We were surprised to find that HSV-1 doesnt just passively wait for the right conditions to reactivate it actively senses danger and takes control of the process, researcher Patryk Krakowiak said.

• #102 Cold Sore Discovery IDs Unknown Trigger for Those Annoying Flare-Ups – Research – Medicine in Motion News

  https://news.med.virginia.edu/research/cold-sore-discovery-ids-unknown-trigger-for-those-annoying-flare-ups/

  Scientists have a new target to prevent cold sores after University of Virginia School of Medicine researchers discovered an unexpected way the herpes virus re-activates in the body. […] The discovery from UVAs Anna Cliffe, PhD, and colleagues seems to defy common sense. She and her team found that the slumbering herpes virus will make a protein to trigger the bodys immune response as part of its escape from dormancy. […] Our findings identify the first viral protein required for herpes simplex virus to wake up from dormancy, and, surprisingly, this protein does so by triggering responses that should act against the virus. […] This is important because it gives us new ways to potentially prevent the virus from waking up and activating immune responses in the nervous system that could have negative consequences in the long term.

• #103 Discovery reveals mechanism that turns herpes virus on and off | Cornell University College of Veterinary Medicine

  https://www.vet.cornell.edu/about-us/news/20191114/discovery-reveals-mechanism-turns-herpes-virus-and

  When the herpes virus enters a cell, the cell tries to protect itself by wrapping the viral DNA tightly around spool-like proteins called histones and condensing it into chromatin, which causes the virus to go dormant. But if the cells are unsuccessful, the chromatin is only loosely bundled, leaving the viral DNA accessible. The virus particles can then turn on their genes and replicate using the cells machinery to start a lytic infection, causing disease. […] In the new study, however, the group showed that the dynamics of the chromatin regulate whether the entire herpes virus genome is turned on, which must occur before any individual genes can be expressed. This new mechanism represents a previously overlooked way to regulate gene expression at the level of the entire viral chromosome. […] Latency and gene regulation is a big problem because we do not know nearly enough about it, said Schang. Its big black box in herpes biology.

• #104 Discovery reveals mechanism that turns herpes virus on and off | Cornell Chronicle

  https://news.cornell.edu/stories/2019/11/discovery-reveals-mechanism-turns-herpes-virus-and

  Most researchers have focused on when and how individual genes on the herpes virus genome are turned on and off during infection to figure out how the virus switches between latent and lytic stages. […] In the new study, however, the group showed that the dynamics of the chromatin regulate whether the entire herpes virus genome is turned on, which must occur before any individual genes can be expressed. […] The discovery opens up new directions for exploring how the virus reactivates after lying dormant.

• #105 Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects | Human Genome Variation

  https://www.nature.com/articles/hgv201424

  Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. […] Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study. […] Viral strain, environmental factors and genetics are believed to account for the observed differences in disease expression among those infected with HSV1. […] Our group previously identified a region of chromosome 21 that is significantly linked to Herpes simplex labialis disease. […] The association of individual SNP genotypes with Herpes simplex labialis frequency was evaluated using linkage analysis and transmission disequilibrium testing.

• #106 Pathogenesis and disease – Human Herpesviruses – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK47449/

  Latency has been recognized biologically since the beginning of the century and has been extensively reviewed. Following entry, both HSV-1 and HSV-2 infect nerve endings and translocate by retrograde transport to the nuclei of sensory ganglia. The virus multiplies in a small number of sensory neurons, which are ultimately destroyed. In the vast majority of the infected neurons, the viral genome remains for the entire life of the individual in an episomal state. In a fraction of individuals, the virus reactivates and is moved by anterograde transport to a site at or near the portal of entry. Reactivations occur following a variety of local or systemic stimuli. […] Little is known regarding the mechanisms by which the virus establishes and maintains a latent state or is reactivated. There are in fact disagreements on the fate of neurons in which latent virus became reactivated. The relevant issues may be summarized as follows. Sensory neurons harboring virus contain nuclear transcripts arising from approximately 8.5 kbp of the sequences flanking the UL sequence. These transcripts are known as the latency associated transcripts or LATs. A shorter region is more abundantly represented in the nuclei. The RNA transcribed from this region forms two populations 2 kbp and 1.5 kbp, respectively, and represents stable introns of an unknown, and relatively unstable transcript. The abundant 2.5 and 1.5 kbp RNA play no role in the establishment or maintenance of the latent state although they may play a role in reactivation.

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