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Veterinary Ophthalmology Jul 2016Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in... (Review)
Review
Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats.
Topics: Animals; Antiviral Agents; Cat Diseases; Cats; Herpesviridae Infections; Humans; Varicellovirus
PubMed: 27091747
DOI: 10.1111/vop.12375 -
Journal of Virology Aug 2023Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to the family and is considered one of the two primary viral etiological factors of feline upper...
Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to the family and is considered one of the two primary viral etiological factors of feline upper respiratory tract disease. In this study, we investigated the entry of FHV-1 into host cells using two models: the AK-D cell line and primary feline skin fibroblasts (FSFs). We employed confocal microscopy, siRNA silencing, and selective inhibitors of various entry pathways. Our observations revealed that the virus enters cells via pH and dynamin-dependent endocytosis, as the infection was significantly inhibited by NHCl, bafilomycin A1, dynasore, and mitmab. Additionally, genistein, nystatin, and filipin treatments, siRNA knock-down of caveolin-1, as well as FHV-1 and caveolin-1 colocalization suggest the involvement of caveolin-mediated endocytosis during the entry process. siRNA knock-down of clathrin heavy chain and analysis of virus particle colocalization with clathrin indicated that clathrin-mediated endocytosis also takes part in the primary cells. This is the first study to systematically examine FHV-1 entry into host cells, and for the first time, we describe FHV-1 replication in AK-D and FSFs. IMPORTANCE Feline herpesvirus 1 (FHV-1) is one of the most prevalent viruses in cats, causing feline viral rhinotracheitis, which is responsible for over half of viral upper respiratory diseases in cats and can lead to ocular lesions resulting in loss of sight. Although the available vaccine reduces the severity of the disease, it does not prevent infection or limit virus shedding. Despite the clinical relevance, the entry mechanisms of FHV-1 have not been thoroughly studied. Considering the limitations of commonly used models based on immortalized cells, we sought to verify our findings using primary feline skin fibroblasts, the natural target for infection in cats.
Topics: Animals; Cats; Cat Diseases; Caveolin 1; Clathrin; Endocytosis; Herpesviridae Infections; RNA, Small Interfering; Varicellovirus
PubMed: 37493545
DOI: 10.1128/jvi.00681-23 -
Cellular Microbiology Dec 2021Canid herpesvirus 1 (CHV-1) is a Varicellovirus that causes self-limiting infections in adult dogs but morbidity and mortality in puppies. Using a multipronged approach,...
Entry of the Varicellovirus Canid herpesvirus 1 into Madin-Darby canine kidney epithelial cells is pH-independent and occurs via a macropinocytosis-like mechanism but without increase in fluid uptake.
Canid herpesvirus 1 (CHV-1) is a Varicellovirus that causes self-limiting infections in adult dogs but morbidity and mortality in puppies. Using a multipronged approach, we discovered the CHV-1 entry pathway into Madin-Darby canine kidney (MDCK) epithelial cells. We found that CHV-1 triggered extensive host cell membrane lamellipodial ruffling and rapid internalisation of virions in large, uncoated vacuoles, suggestive of macropinocytosis. Treatment with inhibitors targeting key macropinocytosis factors, including inhibitors of Na /H exchangers, F-actin, myosin light-chain kinase, protein kinase C, p21-activated kinase, phosphatidylinositol-3-kinase and focal adhesion kinase, significantly reduced viral replication. Moreover, the effect was restricted to exposure to the inhibitors early in infection, confirming a role for the macropinocytic machinery during entry. The profile of inhibitors also suggested a role for signalling via integrins and receptor tyrosine kinases in viral entry. In contrast, inhibitors of clathrin, caveolin, microtubules and endosomal acidification did not affect CHV-1 entry into MDCK cells. We found that the virus colocalised with the fluid-phase uptake marker dextran; however, surprisingly, CHV-1 infection did not enhance the uptake of dextran. Thus, our results indicate that CHV-1 uses a macropinocytosis-like, pH-independent entry pathway into MDCK cells, which nevertheless is not based on stimulation of fluid uptake. TAKE AWAYS: CHV-1 enters epithelial cells via a macropinocytosis-like mechanism. CHV-1 induces extensive lamellipodial ruffling. CHV-1 entry into MDCK cells is pH-independent.
Topics: Animals; Cell Line; Dogs; Herpesvirus 1, Canid; Hydrogen-Ion Concentration; Kidney; Madin Darby Canine Kidney Cells; Varicellovirus
PubMed: 34697890
DOI: 10.1111/cmi.13398 -
BMC Genomics Nov 2017The varicelloviruses comprise a genus within the alphaherpesvirus subfamily, and infect both humans and other mammals. Recently, next-generation sequencing has been used...
BACKGROUND
The varicelloviruses comprise a genus within the alphaherpesvirus subfamily, and infect both humans and other mammals. Recently, next-generation sequencing has been used to generate genomic sequences of several members of the Varicellovirus genus. Here, currently available varicellovirus genomic sequences were used for phylogenetic, recombination, and genetic distance analysis.
RESULTS
A phylogenetic network including genomic sequences of individual species, was generated and suggested a potential restriction between the ungulate and non-ungulate viruses. Intraspecies genetic distances were higher in the ungulate viruses (pseudorabies virus (SuHV-1) 1.65%, bovine herpes virus type 1 (BHV-1) 0.81%, equine herpes virus type 1 (EHV-1) 0.79%, equine herpes virus type 4 (EHV-4) 0.16%) than non-ungulate viruses (feline herpes virus type 1 (FHV-1) 0.0089%, canine herpes virus type 1 (CHV-1) 0.005%, varicella-zoster virus (VZV) 0.136%). The G + C content of the ungulate viruses was also higher (SuHV-1 73.6%, BHV-1 72.6%, EHV-1 56.6%, EHV-4 50.5%) compared to the non-ungulate viruses (FHV-1 45.8%, CHV-1 31.6%, VZV 45.8%), which suggests a possible link between G + C content and intraspecies genetic diversity. Varicellovirus clade nomenclature is variable across different species, and we propose a standardization based on genomic genetic distance. A recent study reported no recombination between sequenced FHV-1 strains, however in the present study, both splitstree, bootscan, and PHI analysis indicated recombination. We also found that the recently sequenced Brazilian CHV-1 strain BTU-1 may contain a genetic signal in the UL50 gene from an unknown varicellovirus.
CONCLUSION
Together, the data contribute to a greater understanding of varicellovirus genomics, and we also suggest a new clade nomenclature scheme based on genetic distances.
Topics: Base Composition; Codon; Herpesvirus 1, Bovine; Herpesvirus 1, Equid; Herpesvirus 4, Equid; Mutation; Phylogeny; Recombination, Genetic; Varicellovirus
PubMed: 29157201
DOI: 10.1186/s12864-017-4283-4 -
PLoS Pathogens May 2008Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented...
Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I-restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL 49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL 49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL 49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL 49.5 proteins block TAP as well, these data indicate that UL 49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL 49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL 49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL 49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL 49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL 49.5. Taken together, these results classify the UL 49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
Topics: ATP-Binding Cassette Transporters; Animals; Antigen Presentation; Cattle; Cell Line, Tumor; Cell Survival; Dogs; Herpesvirus 1, Bovine; Herpesvirus 1, Equid; Herpesvirus 1, Suid; Horses; Humans; Protein Transport; Recombination, Genetic; Swine; Transduction, Genetic; Varicellovirus; Viral Envelope Proteins
PubMed: 18516302
DOI: 10.1371/journal.ppat.1000080 -
Current Protocols Jul 2023Our ability to understand the function of the nervous system is dependent upon defining the connections of its constituent neurons. Development of methods to define... (Review)
Review
Our ability to understand the function of the nervous system is dependent upon defining the connections of its constituent neurons. Development of methods to define connections within neural networks has always been a growth industry in the neurosciences. Transneuronal spread of neurotropic viruses currently represents the best means of defining synaptic connections within neural networks. The method exploits the ability of viruses to invade neurons, replicate, and spread through the intimate synaptic connections that enable communication among neurons. Since the method was first introduced in the 1970s, it has benefited from an increased understanding of the virus life cycle, the function of viral genomes, and the ability to manipulate the viral genome in support of directional spread of virus and the expression of transgenes. In this article, we review these advances in viral tracing technology and the ways in which they may be applied for functional dissection of neural networks. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Retrograde infection of CNS circuits by peripheral injection of virus Basic Protocol 2: Transneuronal analysis by intracerebral injection Alternate Protocol 1: Transneuronal analysis with multiple recombinant strains Alternate Protocol 2: Conditional replication and spread of PRV Alternate Protocol 3: Conditional reporters of PRV infection and spread Alternate Protocol 4: Reporters of neural activity in polysynaptic circuits Support Protocol 1: Growing and titering a PRV viral stock Support Protocol 2: Immunohistochemical processing and detection Support Protocol 3: Dual-immunofluorescence localization.
Topics: Animals; Herpesvirus 1, Suid; Neurons
PubMed: 37486157
DOI: 10.1002/cpz1.841 -
Archives of Microbiology Jan 2024Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromes in cattle, including respiratory disease and is one...
Varicellovirus bovinealpha 1 (formerly bovine alphaherpesvirus type 1, BoAHV-1) is associated with several syndromes in cattle, including respiratory disease and is one of the main agents involved in the bovine respiratory disease complex (BRDC). Its infectious cycle is characterized by latent infections with sporadic virus reactivation and transmission. Although the acute disease can be prevented by the use of vaccines, specific therapeutic measures are not available. Ivermectin (IVM) is a semi-synthetic avermectin with a broad-spectrum antiparasitic activity, which has previously shown to have potential as an antiviral drug. In this study, IVM antiviral activity against BoAHV-1 was characterized in two cell lines (MDBK [Madin Darby bovine kidney] and BT [bovine turbinate]), including the measurement of intracellular drug accumulation within virus-infected cells. IVM antiviral activity was assessed at three different drug concentrations (1.25, 2.5 and 5 µM) after incubation for 24, 48 and 72 h. Slight cytotoxicity was only observed with 5 µM IVM. Even the lowest IVM dose was able to induce a significant reduction in virus titers in both cell lines. These findings indicate that the antiviral effects of IVM were evident in our experimental model within the range of concentrations achievable through therapeutic in vivo administration. Consequently, additional in vivo trials are necessary to validate the potential utility of these results in effectively managing BoAHV-1 in infected cattle.
Topics: Animals; Cattle; Ivermectin; Varicellovirus; Antiparasitic Agents; Antiviral Agents
PubMed: 38277061
DOI: 10.1007/s00203-023-03806-3 -
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 Pathology Jan 2015Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses... (Review)
Review
Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation.
Topics: Animals; Biopsy; Disease Models, Animal; Genotype; Herpesviridae Infections; Host-Pathogen Interactions; Humans; Pathology, Molecular; Predictive Value of Tests; Primates; Varicellovirus; Virology; Virulence; Virus Activation; Virus Latency
PubMed: 25255989
DOI: 10.1002/path.4451 -
The Journal of Infectious Diseases Sep 2011
Topics: DNA, Viral; Herpes Zoster; Humans; Neuralgia, Postherpetic; Saliva; Varicellovirus
PubMed: 21849276
DOI: 10.1093/infdis/jir417