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Viruses Sep 2022Herpes Simplex Virus 1 (HSV-1) is a neurotropic human virus that belongs to the subfamily of . Establishment of its productive infection and progression of disease... (Review)
Review
Herpes Simplex Virus 1 (HSV-1) is a neurotropic human virus that belongs to the subfamily of . Establishment of its productive infection and progression of disease pathologies depend largely on successful release of virions from the virus-producing cells. HSV-1 is known to exploit many host factors for its release. Recent studies have shown that heparanase (HPSE) is one such host enzyme that is recruited for this purpose. It is an endoglycosidase that cleaves heparan sulfate (HS) from the surface of infected cells. HS is a virus attachment coreceptor that is commonly found on cell surfaces as HS proteoglycans e.g., syndecan-1 (SDC-1). The current model suggests that HSV-1 during the late stage of infection upregulates HPSE, which in turn enhances viral release by removing the virus-trapping HS moieties. In addition to its role in directly enabling viral release, HPSE accelerates the shedding of HS-containing ectodomains of SDC-1, which enhances HSV-1 release via a similar mechanism by upregulating CREB3 and COPII proteins. This review outlines the role of HPSE and SDC-1 as newly assigned host factors that facilitate HSV-1 release during a lytic infection cycle.
Topics: Humans; Herpesvirus 1, Human; Syndecan-1; Glucuronidase; Heparitin Sulfate
PubMed: 36298711
DOI: 10.3390/v14102156 -
PloS One 2016Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the...
Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154) isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp) and a unique short sequence (7.7 kbp) that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively). The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease.
Topics: Alphaherpesvirinae; Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; Dog Diseases; Dogs; Genes, Viral; Genome, Viral; Hemorrhagic Disorders; Madin Darby Canine Kidney Cells; Open Reading Frames; Sequence Analysis, DNA; Viral Proteins
PubMed: 27213534
DOI: 10.1371/journal.pone.0156015 -
Science China. Life Sciences Aug 2015Chickenpox (varicella) is caused by primary infection with varicella zoster virus (VZV), which can establish long-term latency in the host ganglion. Once reactivated,... (Review)
Review
Chickenpox (varicella) is caused by primary infection with varicella zoster virus (VZV), which can establish long-term latency in the host ganglion. Once reactivated, the virus can cause shingles (zoster) in the host. VZV has a typical herpesvirus virion structure consisting of an inner DNA core, a capsid, a tegument, and an outer envelope. The tegument is an amorphous layer enclosed between the nucleocapsid and the envelope, which contains a variety of proteins. However, the types and functions of VZV tegument proteins have not yet been completely determined. In this review, we describe the current knowledge on the multiple roles played by VZV tegument proteins during viral infection. Moreover, we discuss the VZV tegument protein-protein interactions and their impact on viral tissue tropism in SCID-hu mice. This will help us develop a better understanding of how the tegument proteins aid viral DNA replication, evasion of host immune response, and pathogenesis.
Topics: Animals; Herpes Zoster; Herpesvirus 3, Human; Host-Pathogen Interactions; Humans; Mice, SCID; Viral Proteins; Virion; Virulence; Virus Replication
PubMed: 26208824
DOI: 10.1007/s11427-015-4887-3 -
Viruses Sep 2021An evolutionary arms race occurs between viruses and hosts. Hosts have developed an array of antiviral mechanisms aimed at inhibiting replication and spread of viruses,... (Review)
Review
An evolutionary arms race occurs between viruses and hosts. Hosts have developed an array of antiviral mechanisms aimed at inhibiting replication and spread of viruses, reducing their fitness, and ultimately minimising pathogenic effects. In turn, viruses have evolved sophisticated counter-measures that mediate evasion of host defence mechanisms. A key aspect of host defences is the ability to differentiate between self and non-self. Previous studies have demonstrated significant suppression of CpG and UpA dinucleotide frequencies in the coding regions of RNA and small DNA viruses. Artificially increasing these dinucleotide frequencies results in a substantial attenuation of virus replication, suggesting dinucleotide bias could facilitate recognition of non-self RNA. The interferon-inducible gene, zinc finger antiviral protein (ZAP) is the host factor responsible for sensing CpG dinucleotides in viral RNA and restricting RNA viruses through direct binding and degradation of the target RNA. Herpesviruses are large DNA viruses that comprise three subfamilies, alpha, beta and gamma, which display divergent CpG dinucleotide patterns within their genomes. ZAP has recently been shown to act as a host restriction factor against human cytomegalovirus (HCMV), a beta-herpesvirus, which in turn evades ZAP detection by suppressing CpG levels in the major immediate-early transcript IE1, one of the first genes expressed by the virus. While suppression of CpG dinucleotides allows evasion of ZAP targeting, synonymous changes in nucleotide composition that cause genome biases, such as low GC content, can cause inefficient gene expression, especially in unspliced transcripts. To maintain compact genomes, the majority of herpesvirus transcripts are unspliced. Here we discuss how the conflicting pressures of ZAP evasion, the need to maintain compact genomes through the use of unspliced transcripts and maintaining efficient gene expression may have shaped the evolution of herpesvirus genomes, leading to characteristic CpG dinucleotide patterns.
Topics: Alphaherpesvirinae; Animals; Betaherpesvirinae; Dinucleoside Phosphates; Evolution, Molecular; Gammaherpesvirinae; Gene Expression; Genome, Viral; Herpesviridae; Host-Pathogen Interactions; Humans; Interferons; RNA Splicing; RNA, Viral; RNA-Binding Proteins; Signal Transduction; Viral Proteins
PubMed: 34578438
DOI: 10.3390/v13091857 -
Methods in Molecular Biology (Clifton,... 2020Extracellular vesicles (EVs) are secreted membrane vesicles, derived from endosomes or from the plasma membrane, which have been isolated from most cell types and...
Extracellular vesicles (EVs) are secreted membrane vesicles, derived from endosomes or from the plasma membrane, which have been isolated from most cell types and biological fluids. Although EVs are highly heterogeneous and their classification is complex, two major categories can be distinguished: microvesicles (MVs), which derive from the shedding of the plasma membrane, and exosomes, which correspond to intraluminal vesicles released to the extracellular milieu upon fusion of multivesicular bodies (MVBs) with the plasma membrane. Cells infected with viruses may secrete MVs containing viral proteins, RNAs and, in some instances, infectious virions. A recent study carried out by our laboratory has shown that MVs released by cells infected with HSV-1 contained virions and were endocytosed by naïve cells leading to a productive infection. This suggests that HSV-1 may use MVs for spreading, expanding its tropism and evading the host immune response. Here we describe in detail the methods used to isolate and analyse the MVs released from HSV-1-infected cells.
Topics: Cell Line; Cell-Derived Microparticles; Herpes Simplex; Herpesvirus 1, Human; Humans
PubMed: 31617186
DOI: 10.1007/978-1-4939-9814-2_17 -
Viruses Nov 2020Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67%... (Review)
Review
Herpes simplex viruses (HSVs) are neurotropic viruses with broad host range whose infections cause considerable health problems in both animals and humans. In fact, 67% of the global population under the age of 50 are infected with HSV-1 and 13% have clinically recurrent HSV-2 infections. The most prescribed antiherpetics are nucleoside analogues such as acyclovir, but the emergence of mutants resistant to these drugs and the lack of available vaccines against human HSVs has led to an imminent need for new antivirals. Valproic acid (VPA) is a branched short-chain fatty acid clinically used as a broad-spectrum antiepileptic drug in the treatment of neurological disorders, which has shown promising antiviral activity against some herpesviruses. Moreover, its amidic derivatives valpromide and valnoctamide also share this antiherpetic activity. This review summarizes the current research on the use of VPA and its amidic derivatives as alternatives to traditional antiherpetics in the fight against HSV infections.
Topics: Alphaherpesvirinae; Amides; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Valproic Acid
PubMed: 33256172
DOI: 10.3390/v12121356 -
Frontiers in Immunology 2021In the process of infecting the host, alphaherpesviruses have derived a series of adaptation and survival strategies, such as latent infection, autophagy and immune... (Review)
Review
In the process of infecting the host, alphaherpesviruses have derived a series of adaptation and survival strategies, such as latent infection, autophagy and immune evasion, to survive in the host environment. Infected cell protein 22 (ICP22) or its homologue immediate early protein 63 (IE63) is a posttranslationally modified multifunctional viral regulatory protein encoded by all alphaherpesviruses. In addition to playing an important role in the efficient use of host cell RNA polymerase II, it also plays an important role in the defense process of the virus overcoming the host immune system. These two effects of ICP22/IE63 are important survival strategies for alphaherpesviruses. In this review, we summarize the complex mechanism by which the ICP22 protein regulates the transcription of alphaherpesviruses and their host genes and the mechanism by which ICP22/IE63 participates in immune escape. Reviewing these mechanisms will also help us understand the pathogenesis of alphaherpesvirus infections and provide new strategies to combat these viral infections.
Topics: Alphaherpesvirinae; Animals; Gene Expression Regulation, Viral; Herpesviridae Infections; Humans; Immediate-Early Proteins; Immune Evasion
PubMed: 34925320
DOI: 10.3389/fimmu.2021.743466 -
Archives of Virology Sep 2015The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to...
The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to inhibit herpes simplex virus (HSV) replication, which is associated with skin and epithelial mucosa infections. The treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. Based on this evidence, the aim of this study was to investigate the anti-HSV effects of soybean isoflavonoids: daidzein, genistein, glycitein, and coumestrol. Genistein and coumestrol inhibited HSV-1 (KOS and 29R strains, which are acyclovir sensitive and acyclovir resistant, respectively) and HSV-2 (333 strain) replication, whereas no antiviral effects were detected for daidzein and glycitein. The mechanisms of action were evaluated by different methodological strategies. Coumestrol affected the early stages of viral infection, and both compounds were able to reduce HSV-1 protein expression, as well as HSV-2 cell-to-cell spread.
Topics: Antiviral Agents; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Isoflavones; Glycine max; Virus Replication
PubMed: 26156104
DOI: 10.1007/s00705-015-2514-z -
Antimicrobial Agents and Chemotherapy Mar 2021Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and...
Herpesviruses are widespread and can cause serious illness. Many currently available antiviral drugs have limited effects, result in rapid development of resistance, and often exhibit dose-dependent toxicity. Especially for human cytomegalovirus (HCMV), new well-tolerated compounds with novel mechanisms of action are urgently needed. In this study, we characterized the antiviral activity of two new diazadispiroalkane derivatives, 11826091 and 11826236. These two small molecules exhibited strong activity against low-passage-number HCMV. Pretreatment of cell-free virus with these compounds greatly reduced infection. Time-of-addition assays where 11826091 or 11826236 was added to cells before infection, before and during infection, or during or after infection demonstrated an inhibitory effect on early steps of infection. Interestingly, 11826236 had an effect by addition to cells after infection. Results from entry assays showed the major effect to be on attachment. Only 11826236 had a minimal effect on penetration comparable to heparin. Further, no effect on virus infection was found for cell lines with a defect in heparan sulfate expression or lacking all surface glycosaminoglycans, indicating that these small molecules bind to heparan sulfate on the cell surface. To test this further, we extended our analyses to pseudorabies virus (PrV), a member of the , which is known to use cell surface heparan sulfate for initial attachment via nonessential glycoprotein C (gC). While infection with PrV wild type was strongly impaired by 11826091 or 11826236, as with heparin, a mutant lacking gC was unaffected by either treatment, demonstrating that primary attachment to heparan sulfate via gC is targeted by these small molecules.
Topics: Alkanes; Animals; Antiviral Agents; Glycosaminoglycans; Heparin; Heparitin Sulfate; Herpesvirus 1, Suid; Humans; Spiro Compounds; Viral Envelope Proteins; Virus Internalization
PubMed: 33495228
DOI: 10.1128/AAC.02103-20 -
FEMS Microbiology Letters Jun 2018
Topics: History, 20th Century; History, 21st Century; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus; Viral Tropism
PubMed: 29873707
DOI: 10.1093/femsle/fny019