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Journal of Korean Medical Science May 2018
Topics: Atrial Fibrillation; Case-Control Studies; Herpes Zoster; Herpesvirus 3, Human; Humans
PubMed: 29805342
DOI: 10.3346/jkms.2018.33.e181 -
Viruses Apr 2022The present study generated nectin1-mutant mice with single amino acid substitution and tested the anti-pseudorabies virus (PRV) ability of the mutant mice, with the aim...
The present study generated nectin1-mutant mice with single amino acid substitution and tested the anti-pseudorabies virus (PRV) ability of the mutant mice, with the aim to establish a model for PRV-resistant livestock. A phenylalanine to alanine transition at position 129 (F129A) of nectin1 was introduced into the mouse genome to generate nectin1 (F129A) mutant mice. The mutant mice were infected with a field-isolated highly virulent PRV strain by subcutaneous injection of virus. We found that the homozygous mutant mice had significantly alleviated disease manifestations and decreased death rate and viral loading in serum and tissue compared with heterozygous mutant and wild-type mice. In addition to disease resistance, the homozygous mutant mice showed a defect in eye development, indicating the side effect on animals by only one amino acid substitution in nectin1. Results demonstrate that gene modification in nectin1 is an effective approach to confer PRV resistance on animals, but the mutagenesis pattern requires further investigation to increase viral resistance without negative effect on animal development.
Topics: Animals; Herpesvirus 1, Suid; Mice
PubMed: 35632616
DOI: 10.3390/v14050874 -
BMC Veterinary Research Feb 2024Varicellovirus equidalpha1 (formerly Equid alphaherpesvirus 1, EqAHV-1) is among the most important viruses responsible for respiratory disease outbreaks among horses...
BACKGROUND
Varicellovirus equidalpha1 (formerly Equid alphaherpesvirus 1, EqAHV-1) is among the most important viruses responsible for respiratory disease outbreaks among horses throughout the world. No reports to date have detailed the association between EqAHV-1 and respiratory disease among horses in China. This study described one such outbreak among a population of horses in north Xinjiang that occurred from April 2021 - May 2023.
RESULTS
qPCR revealed that EqAHV-1 was detectable in all samples and this virus was identified as a possible source of respiratory disease, although a limited subset of these samples were also positive for EqAHV-2, EqAHV-4, and EqAHV-5. In total, three EqAHV-1 strains responsible for causing respiratory illness in horses were isolated successfully, and full-length ORF33 sequence comparisonsand phylogenetic analyses indicated that these isolates may have originated from EqAHV-1 strains detected in Yili horse abortions. ORF30 sequence data additionally suggested that these strains were neuropathic, as evidenced by the presence of a guanine residue at nucleotide position 2254 corresponding to the aspartic acid present at position 752 in the DNA polymerase encoded by this virus.
CONCLUSION
This study is the first report of an outbreak of respiratory disease among horses in China caused by EqAHV-1. ORF30 sequence characterization revealed that these EqAHV-1 strains harbored a neuropathogenic genotype. Given the detection of this virus in horses suffering from respiratory disease, concern is warranted with respect to this neuropathogenic EqAHV-1 outbreak.
Topics: Pregnancy; Female; Horses; Animals; Varicellovirus; Phylogeny; DNA, Viral; Herpesvirus 1, Equid; Disease Outbreaks; Horse Diseases; Herpesviridae Infections
PubMed: 38413936
DOI: 10.1186/s12917-024-03925-z -
The Journal of General Virology Apr 2010Varicella-zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been... (Review)
Review
A proposal for a common nomenclature for viral clades that form the species varicella-zoster virus: summary of VZV Nomenclature Meeting 2008, Barts and the London School of Medicine and Dentistry, 24-25 July 2008.
Varicella-zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been licensed and widely used. Three groups have published genotyping schemes based on single nucleotide polymorphisms (SNPs) and, between them, have identified five distinct phylogenetic clades, with an additional two putative clades. Sequencing of over 23 whole VZV genomes from around the world further refined the phylogenetic distinctions between SNP genotypes. Widespread surveillance in countries in which the varicella vaccine is now in use and the difficulties posed by three unique genotyping approaches prompted an international meeting, at which a common nomenclature based on phylogenetic clades was agreed upon. In this paper, we review the original genotyping schemes and discuss the basis for a novel common nomenclature for VZV strains. We propose a minimum set of SNPs that we recommend should be used to genotype these viruses. Finally, we suggest criteria by which novel clades can be recognized.
Topics: Genome, Viral; Genotype; Herpesvirus 3, Human; Humans; Phylogeny; Polymorphism, Single Nucleotide; Terminology as Topic
PubMed: 20071486
DOI: 10.1099/vir.0.017814-0 -
MBio Jun 2016Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy...
UNLABELLED
Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV) exocytosis, based on total internal reflection fluorescence (TIRF) microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (ii) exocytosis of viral light particles, and (iii) exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway.
IMPORTANCE
The alphaherpesviruses, including the important human pathogens herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), are among the few viruses that have evolved to exploit the mammalian nervous system. These viruses typically cause mild recurrent herpetic or zosteriform lesions but can also cause debilitating herpes encephalitis, more frequently in very young, old, immunocompromised, or nonnatural hosts. Importantly, many of the molecular and cellular mechanisms of viral assembly and egress remain unclear. This study addresses the trafficking of viral glycoproteins to the plasma membrane, exocytosis of light particles, and exocytosis of virions. Trafficking of glycoproteins affects immune evasion and pathogenesis and may precede virus particle assembly. The release of light particles may also contribute to immune evasion and pathogenesis. Finally, exocytosis of virions is important to understand, as this final step in the virus replication cycle produces infectious extracellular particles capable of spreading to the next round of host cells.
Topics: Animals; Biological Transport; Cell Line; Cell Membrane; Exocytosis; Fluorescent Dyes; Glycoproteins; Herpesvirus 1, Human; Herpesvirus 1, Suid; Herpesvirus 2, Human; Humans; Hydrogen-Ion Concentration; Immune Evasion; Microscopy, Fluorescence; Protein Transport; Sus scrofa; Viral Envelope Proteins; Virion; Virus Assembly; rab GTP-Binding Proteins
PubMed: 27273828
DOI: 10.1128/mBio.00820-16 -
Journal of Microbiology (Seoul, Korea) Jan 2019Harringtonine (HT) and homoharringtonine (HHT), alkaloid esters isolated from the genus Cephalotaxus, exhibit antitumor activity. A semisynthetic HHT has been approved...
Harringtonine (HT) and homoharringtonine (HHT), alkaloid esters isolated from the genus Cephalotaxus, exhibit antitumor activity. A semisynthetic HHT has been approved for treatment of chronic myelogenous leukemia. In addition to antileukemic activity, HT and HHT are reported to possess potent antiviral activity. In this study, we investigated the effects of HT and HHT on replication of varicella-zoster virus (VZV) in vitro. HT and HHT, but not their biologically inactive parental alkaloid cephalotaxine (CET), significantly inhibited replication of recombinant VZV-pOka luciferase. Furthermore, HT and HHT, but not CET, strongly induced down-regulation of VZV lytic genes and exerted potent antiviral effects against a VZV clinical isolate. The collective data support the utility of HT and HHT as effective antiviral candidates for treatment of VZV-associated diseases.
Topics: Antiviral Agents; Cephalotaxus; Esters; Harringtonines; Herpesvirus 3, Human; Homoharringtonine; Humans; Plant Extracts; Virus Replication
PubMed: 30456755
DOI: 10.1007/s12275-019-8514-z -
Viruses May 2015In this study we identified two 3'-coterminal RNA molecules in the pseudorabies virus. The highly abundant short transcript (CTO-S) proved to be encoded between the ul21...
In this study we identified two 3'-coterminal RNA molecules in the pseudorabies virus. The highly abundant short transcript (CTO-S) proved to be encoded between the ul21 and ul22 genes in close vicinity of the replication origin (OriL) of the virus. The less abundant long RNA molecule (CTO-L) is a transcriptional readthrough product of the ul21 gene and overlaps OriL. These polyadenylated RNAs were characterized by ascertaining their nucleotide sequences with the Illumina HiScanSQ and Pacific Biosciences Real-Time (PacBio RSII) sequencing platforms and by analyzing their transcription kinetics through use of multi-time-point Real-Time RT-PCR and the PacBio RSII system. It emerged that transcription of the CTOs is fully dependent on the viral transactivator protein IE180 and CTO-S is not a microRNA precursor. We propose an interaction between the transcription and replication machineries at this genomic location, which might play an important role in the regulation of DNA synthesis.
Topics: Gene Expression Profiling; Herpesvirus 1, Suid; High-Throughput Nucleotide Sequencing; RNA, Viral; Real-Time Polymerase Chain Reaction; Transcription, Genetic; Virus Replication
PubMed: 26008709
DOI: 10.3390/v7052727 -
PloS One 2022Bovine respiratory disease (BRD) is the costliest complex disease affecting the cattle industry worldwide, with significant economic losses. BRD pathogenesis involves...
Bovine respiratory disease (BRD) is the costliest complex disease affecting the cattle industry worldwide, with significant economic losses. BRD pathogenesis involves several interactions between microorganisms, such as bacteria and viruses, and management factors. The present study aimed to characterize the nasal virome from 43 pooled nasal swab samples collected from Egyptian nonvaccinated cow-calf operations with acute BRD from January to February 2020 using metagenomic sequencing. Bovine herpesvirus-1 (BHV-1), first detection of bovine herpesvirus-5 (BHV-5), and first detection of bovine parvovirus-3 (BPV-3) were the most commonly identified in Egyptian cattle. Moreover, phylogenetic analysis of glycoprotein B revealed that the BHV-1 isolate is closely related to the Cooper reference strain (genotype 1.1), whereas the BHV-5 isolate is closely related to the reference virus GenBank NP_954920.1. In addition, the whole-genome sequence of BPV-3 showed 93.02% nucleotide identity with the reference virus GenBank AF406967.1. In this study, several DNA viruses, such as BHV-1 and first detection BHV-5, and BPV-3, were detected and may have an association with the BRD in Egyptian cattle. Therefore, further research, including investigating more samples from different locations to determine the prevalence of detected viruses and their contributions to BRD in cattle in Egypt, is needed.
Topics: Animals; Cattle; Cattle Diseases; Female; Herpesvirus 1, Bovine; Herpesvirus 5, Bovine; Phylogeny; Respiratory Tract Diseases; Virome; Viruses
PubMed: 35511760
DOI: 10.1371/journal.pone.0267036 -
Journal of Virology Jan 2018Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio than herpes...
Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio than herpes simplex virus (HSV). In contrast, VZV is highly infectious by airborne transmission. Neurons are major targets for VZV ; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens. Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human neurons than in other cell types and that the number of total virus genomes relative to the number of viral particles that can form plaques in culture is much lower in human neurons than other cultured cells. These findings indicate that human neurons may be useful for studying VZV , for growing preparations of virus with high titers, and for isolating the virus from human samples.
Topics: Cell Line; Cells, Cultured; Fibroblasts; Genome, Viral; Herpesvirus 3, Human; Human Embryonic Stem Cells; Humans; Microscopy, Electron; Neurons; Virology; Virus Activation; Virus Latency; Virus Replication
PubMed: 29046461
DOI: 10.1128/JVI.01108-17 -
Journal of Virology Jan 2018Conserved across the family , glycoprotein B (gB) is responsible for driving fusion of the viral envelope with the host cell membrane for entry upon receptor binding and...
Conserved across the family , glycoprotein B (gB) is responsible for driving fusion of the viral envelope with the host cell membrane for entry upon receptor binding and activation by the viral gH/gL complex. Although crystal structures of the gB ectodomains of several herpesviruses have been reported, the membrane fusion mechanism has remained elusive. Here, we report the X-ray structure of the pseudorabies virus (PrV) gB ectodomain, revealing a typical class III postfusion trimer that binds membranes via its fusion loops (FLs) in a cholesterol-dependent manner. Mutagenesis of FL residues allowed us to dissect those interacting with distinct subregions of the lipid bilayer and their roles in membrane interactions. We tested 15 gB variants for the ability to bind to liposomes and further investigated a subset of them in functional assays. We found that PrV gB FL residues Trp187, Tyr192, Phe275, and Tyr276, which were essential for liposome binding and for fusion in cellular and viral contexts, form a continuous hydrophobic patch at the gB trimer surface. Together with results reported for other alphaherpesvirus gBs, our data suggest a model in which Phe275 from the tip of FL2 protrudes deeper into the hydrocarbon core of the lipid bilayer, while the side chains of Trp187, Tyr192, and Tyr276 form a rim that inserts into the more superficial interfacial region of the membrane to catalyze the fusion process. Comparative analysis with gBs from beta- and gamma-herpesviruses suggests that this membrane interaction model is valid for gBs from all herpesviruses. Herpesviruses are common human and animal pathogens that infect cells by entering via fusion of viral and cellular membranes. Central to the membrane fusion event is glycoprotein B (gB), which is the most conserved envelope protein across the herpesvirus family. Like other viral fusion proteins, gB anchors itself in the target membrane via two polypeptide segments called fusion loops (FLs). The molecular details of how gB FLs insert into the lipid bilayer have not been described. Here, we provide structural and functional data regarding key FL residues of gB from pseudorabies virus, a porcine herpesvirus of veterinary concern, which allows us to propose, for the first time, a molecular model to understand how the initial interactions by gBs from all herpesviruses with target membranes are established.
Topics: Binding Sites; Crystallography, X-Ray; Herpesvirus 1, Suid; Liposomes; Models, Molecular; Mutation; Protein Binding; Protein Conformation; Protein Domains; Viral Envelope Proteins; Virus Internalization
PubMed: 29046441
DOI: 10.1128/JVI.01203-17