-
Viruses Jan 2022Primate simplex viruses, including Herpes simplex viruses 1 and 2, form a group of closely related herpesviruses, which establish latent infections in neurons of their...
Primate simplex viruses, including Herpes simplex viruses 1 and 2, form a group of closely related herpesviruses, which establish latent infections in neurons of their respective host species. While neuropathogenic infections in their natural hosts are rare, zoonotic transmission of Macacine alphaherpesvirus 1 (McHV1) from macaques to humans is associated with severe disease. Human infections with baboon-derived Papiine alphaherpesvirus 2 (PaHV2) have not been reported, although PaHV2 and McHV1 share several biological properties, including neuropathogenicity in mice. The reasons for potential differences in PaHV2 and McHV1 pathogenicity are presently not understood, and answering these questions will require mutagenic analysis. Here, we report the development of a recombinant system, which allows rescue of recombinant PaHV2. In addition, we used recombineering to generate viruses carrying reporter genes (Gaussia luciferase or enhanced green fluorescent protein), which replicate with similar efficiency as wild-type PaHV2. We demonstrate that these viruses can be used to analyze susceptibility of cells to infection and inhibition of infection by neutralizing antibodies and antiviral compounds. In summary, we created a recombinant system for PaHV2, which in the future will be invaluable for molecular analyses of neuropathogenicity of PaHV2.
Topics: Animals; Antibodies, Viral; Antiviral Agents; Cell Line; Cloning, Molecular; Genes, Reporter; Genome, Viral; Humans; Papio; Recombination, Genetic; Simplexvirus
PubMed: 35062295
DOI: 10.3390/v14010091 -
Journal of Virology Jan 2020During herpes simplex virus (HSV) latency, the viral genome is harbored in peripheral neurons in the absence of infectious virus but with the potential to restart... (Review)
Review
During herpes simplex virus (HSV) latency, the viral genome is harbored in peripheral neurons in the absence of infectious virus but with the potential to restart infection. Advances in epigenetics have helped explain how viral gene expression is largely inhibited during latency. Paradoxically, at the same time, the view that latency is entirely silent has been eroding. This low-level noise has implications for our understanding of HSV latency and should not be ignored.
Topics: Animals; Disease Models, Animal; Epigenesis, Genetic; Gene Expression Regulation, Viral; Genome, Viral; Herpes Simplex; Herpesvirus 1, Human; Humans; Neurons; Simplexvirus; Transcription, Genetic; Virus Activation; Virus Latency; Virus Replication
PubMed: 31776275
DOI: 10.1128/JVI.01701-19 -
Virology May 2015Upon infection, the genomes of herpesviruses undergo a striking transition from a non-nucleosomal structure to a chromatin structure. The rapid assembly and modulation... (Review)
Review
Upon infection, the genomes of herpesviruses undergo a striking transition from a non-nucleosomal structure to a chromatin structure. The rapid assembly and modulation of nucleosomes during the initial stage of infection results in an overlay of complex regulation that requires interactions of a plethora of chromatin modulation components. For herpes simplex virus, the initial chromatin dynamic is dependent on viral and host cell transcription factors and coactivators that mediate the balance between heterochromatic suppression of the viral genome and the euchromatin transition that allows and promotes the expression of viral immediate early genes. Strikingly similar to lytic infection, in sensory neurons this dynamic transition between heterochromatin and euchromatin governs the establishment, maintenance, and reactivation from the latent state. Chromatin dynamics in both the lytic infection and latency-reactivation cycles provides opportunities to shift the balance using small molecule epigenetic modulators to suppress viral infection, shedding, and reactivation from latency.
Topics: Chromatin; Epigenesis, Genetic; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Simplexvirus; Transcription Factors; Virus Latency; Virus Replication
PubMed: 25702087
DOI: 10.1016/j.virol.2015.01.026 -
Virologica Sinica Dec 2012Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2. The prevalence of HSV is worldwide. It primarily infects humans... (Review)
Review
Herpes simplex virus (HSV) is a group of common human pathogens with two serotypes HSV-1 and HSV-2. The prevalence of HSV is worldwide. It primarily infects humans through epithelial cells, when it introduces a latent infection into the nervous system. During viral latency, only a region known as the latency-associated transcript (LAT) is expressed. The discovery of HSV miRNAs helps to draw a larger picture of the infection and pathogenesis of the virus. This review summarizes miRNAs found in HSV-1 and HSV-2 so far. The functional studies of miRNAs in HSV to date indicate that they play a stage-specific role coordinated with viral proteins to maintain the virus life cycle.
Topics: Gene Expression Regulation, Viral; Humans; MicroRNAs; RNA, Viral; Simplexvirus; Virus Latency; Virus Replication
PubMed: 23180288
DOI: 10.1007/s12250-012-3266-5 -
Cold Spring Harbor Perspectives in... Sep 2012Herpes simplex virus (HSV) encodes seven proteins necessary for viral DNA synthesis-UL9 (origin-binding protein), ICP8 (single-strand DNA [ssDNA]-binding protein),... (Review)
Review
Herpes simplex virus (HSV) encodes seven proteins necessary for viral DNA synthesis-UL9 (origin-binding protein), ICP8 (single-strand DNA [ssDNA]-binding protein), UL30/UL42 (polymerase), and UL5/UL8/UL52 (helicase/primase). It is our intention to provide an up-to-date analysis of our understanding of the structures of these replication proteins and how they function during HSV replication. The potential roles of host repair and recombination proteins will also be discussed.
Topics: DNA Replication; DNA-Directed DNA Polymerase; Genome, Viral; Models, Genetic; Protein Structure, Tertiary; Replication Origin; Simplexvirus; Viral Proteins; Virus Replication
PubMed: 22952399
DOI: 10.1101/cshperspect.a013011 -
Uirusu Dec 2010Herpes simplex virus (HSV), the prototype of the herpesvirus family, causes a variety of diseases in human. In this review, I focus on the molecular mechanism of HSV... (Review)
Review
Herpes simplex virus (HSV), the prototype of the herpesvirus family, causes a variety of diseases in human. In this review, I focus on the molecular mechanism of HSV infection including recent advance on this research field.
Topics: Animals; Cell Nucleus; Cytoplasm; DNA, Viral; Genes, Viral; Glycoproteins; Humans; Simplexvirus; Transcription, Genetic; Viral Envelope Proteins; Virion; Virus Latency; Virus Replication
PubMed: 21488332
DOI: 10.2222/jsv.60.187 -
Virology Journal May 2016Human herpes simplex virus (HSV) is a ubiquitous human pathogen that establishes a lifelong latent infection and is associated with mucocutaneous lesions. In... (Review)
Review
Human herpes simplex virus (HSV) is a ubiquitous human pathogen that establishes a lifelong latent infection and is associated with mucocutaneous lesions. In multicellular organisms, cell death is a crucial host defense mechanism that eliminates pathogen-infected cells. Apoptosis is a well-defined form of programmed cell death executed by a group of cysteine proteases, called caspases. Studies have shown that HSV has evolved strategies to counteract caspase activation and apoptosis by encoding anti-apoptotic viral proteins such as gD, gJ, Us3, LAT, and the ribonucleotide reductase large subunit (R1). Recently, necroptosis has been identified as a regulated form of necrosis that can be invoked in the absence of caspase activity. Receptor-interacting kinase 3 (RIP3 or RIPK3) has emerged as a central signaling molecule in necroptosis; it is activated via interaction with other RIP homotypic interaction motif (RHIM)-containing proteins such as RIP1 (or RIPK1). There is increasing evidence that HSV R1 manipulates necroptosis via the RHIM-dependent inactivation or activation ofRIP3 in a species-specific manner. This review summarizes the current understanding of the interplay between HSV infection and cell death pathways, with an emphasis on apoptosis and necroptosis.
Topics: Apoptosis; Apoptosis Regulatory Proteins; Cell Death; Host-Pathogen Interactions; Humans; Immune Evasion; Simplexvirus; Viral Proteins
PubMed: 27154074
DOI: 10.1186/s12985-016-0528-0 -
Frontiers in Bioscience (Scholar... Jan 2010Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) are two important human pathogens that belong to the genus simplex within the subfamily alpha of the... (Review)
Review
Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) are two important human pathogens that belong to the genus simplex within the subfamily alpha of the Herpesvirinae. Toll-like receptors (TLRs) constitute a family of conserved sensors that play a prominent role during the early anti-viral response, including that against herpesviruses. Although substantial progress has been made, central questions remain to be solved to figure out how TLRs modulate viral pathogenesis. The aim of the present report is to review the current knowledge about TLR recognition and signaling of herpesviruses, focusing on HSV infection. The relative contribution of the TLR-mediated immune responses to antiviral immunity versus viral pathogenesis will be discussed as well.
Topics: Aminoquinolines; Animals; Cytokines; Herpes Simplex; Humans; Imidazoles; Imiquimod; Mice; Signal Transduction; Simplexvirus; Toll-Like Receptors
PubMed: 20036979
DOI: 10.2741/s96 -
Journal of Virology Nov 2023Immune evasion and latency are key mechanisms that underlie the success of herpesviruses. In each case, interactions between viral and host proteins are required and due...
Immune evasion and latency are key mechanisms that underlie the success of herpesviruses. In each case, interactions between viral and host proteins are required and due to co-evolution, not all mechanisms are preserved across host species, even if infection is possible. This is highlighted by the herpes simplex virus (HSV) protein immediate early-infected cell protein (ICP)47, which inhibits the detection of infected cells by killer T cells and acts with high efficiency in humans, but poorly, if at all in mouse cells. Here, we show that ICP47 retains modest but detectable function in mouse cells, but in an model we found no role during acute infection or latency. We also explored the activity of the ICP47 promoter, finding that it could be active during latency, but this was dependent on genome location. These results are important to interpret HSV pathogenesis work done in mice.
Topics: Animals; Mice; Herpes Simplex; Immediate-Early Proteins; Immune Evasion; Promoter Regions, Genetic; Simplexvirus; Viral Proteins; Virus Latency
PubMed: 37902400
DOI: 10.1128/jvi.01107-23 -
Human Gene Therapy Feb 2014
Review
Topics: Genetic Therapy; Genetic Vectors; Humans; Simplexvirus
PubMed: 24502405
DOI: 10.1089/hum.2014.2501