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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 -
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 -
Frontiers in Immunology 2024Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function... (Review)
Review
Type I interferons (IFN-I) are key immune messenger molecules that play an important role in viral defense. They act as a bridge between microbe sensing, immune function magnitude, and adaptive immunity to fight infections, and they must therefore be tightly regulated. It has become increasingly evident that thymic irregularities and mutations in immune genes affecting thymic tolerance can lead to the production of IFN-I autoantibodies (autoAbs). Whether these biomarkers affect the immune system or tissue integrity of the host is still controversial, but new data show that IFN-I autoAbs may increase susceptibility to severe disease caused by certain viruses, including SARS-CoV-2, herpes zoster, and varicella pneumonia. In this article, we will elaborate on disorders that have been identified with IFN-I autoAbs, discuss models of how tolerance to IFN-Is is lost, and explain the consequences for the host.
Topics: Autoantibodies; Thymus Gland; Interferon Type I; Herpesvirus 3, Human
PubMed: 38455040
DOI: 10.3389/fimmu.2024.1327784 -
Virologica Sinica Aug 2023• Cells infected with HSV-2 release migrasomes containing HSV-2 virions. • HSV-2 in the isolated migrasomes can be transmitted to uninfected cells and cause...
• Cells infected with HSV-2 release migrasomes containing HSV-2 virions. • HSV-2 in the isolated migrasomes can be transmitted to uninfected cells and cause productive infection. • It is the first time that migrasomes have been found to play a role in virus spread.
Topics: Animals; Chlorocebus aethiops; Herpesvirus 2, Human; Cell Line; Vero Cells
PubMed: 37295496
DOI: 10.1016/j.virs.2023.06.001 -
Epidemiology and Infection Feb 2023Herpes simplex virus type 1 (HSV-1) infection is a lifelong infection that is acquired primarily orally and during childhood. We aimed to characterise HSV-1 epidemiology... (Meta-Analysis)
Meta-Analysis Review
Herpes simplex virus type 1 (HSV-1) infection is a lifelong infection that is acquired primarily orally and during childhood. We aimed to characterise HSV-1 epidemiology in Australia and New Zealand. HSV-1-related data as recent as 6 December 2021 were systematically reviewed, synthesised and reported, following PRISMA guidelines. Pooled mean seroprevalence and proportions of HSV-1 detection in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. HSV-1 measures were retrieved from 21 eligible publications. Extracted HSV-1 measures included 13 overall seroprevalence measures (27 stratified) in Australia, four overall proportions of HSV-1 detection in clinically diagnosed GUD (four stratified) in Australia, and ten overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (26 stratified) in Australia and New Zealand. Pooled mean seroprevalence among healthy adults in Australia was 84.8% (95% confidence interval (CI) 74.3-93.1%). Pooled mean seroprevalence was 70.2% (95% CI 47.4-88.7%) among individuals <35 years of age and 86.9% (95% CI 79.3-93.0%) among individuals ≥35 years. Seroprevalence increased by 1.05-fold (95% CI 1.01-1.10) per year. Pooled mean proportion of HSV-1 detection in GUD was 8.2% (95% CI 0.4-22.9%). Pooled mean proportion of HSV-1 detection in genital herpes was 30.5% (95% CI 23.3-38.3%), and was highest in young individuals. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI 1.00-1.08) per year. Included studies showed heterogeneity, but 30% of the heterogeneity in seroprevalence and 42% of the heterogeneity in proportion of HSV-1 detection in genital herpes were explained in terms of epidemiological factors. HSV-1 seroprevalence is higher in Australia than in other Western countries. HSV-1 epidemiology in Australia and New Zealand appears to be transitioning towards less oral acquisition in childhood, but more genital acquisition among youth.
Topics: Adolescent; Adult; Aged, 80 and over; Humans; Australia; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; New Zealand; Seroepidemiologic Studies
PubMed: 36750224
DOI: 10.1017/S0950268823000183 -
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 -
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 -
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 -
Cell Reports May 2022The presence and abundance of viral proteins within host cells are part of the essential signatures of the cellular stages of viral infections. However, methods that can...
The presence and abundance of viral proteins within host cells are part of the essential signatures of the cellular stages of viral infections. However, methods that can comprehensively detect and quantify these proteins are still limited, particularly for viruses with large protein coding capacity. Here, we design and experimentally validate a mass spectrometry-based Targeted herpesviRUS proTEin Detection (TRUSTED) assay for monitoring human viruses representing the three Herpesviridae subfamilies-herpes simplex virus type 1, human cytomegalovirus (HCMV), and Kaposi sarcoma-associated herpesvirus. We demonstrate assay applicability for (1) capturing the temporal cascades of viral replication, (2) detecting proteins throughout a range of virus concentrations and in in vivo models of infection, (3) assessing the effects of clinical therapeutic agents and sirtuin-modulating compounds, (4) studies using different laboratory and clinical viral strains, and (5) discovering a role for carbamoyl phosphate synthetase 1 in supporting HCMV replication.
Topics: Cytomegalovirus; Herpesvirus 1, Human; Herpesvirus 8, Human; Humans; Mass Spectrometry; Virus Replication
PubMed: 35545036
DOI: 10.1016/j.celrep.2022.110810 -
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