-
Trends in Molecular Medicine Mar 2008Several neuroinvasive viruses can be used to study the mammalian nervous system. In particular, infection by pseudorabies virus (PRV), an alpha-herpesvirus with broad... (Review)
Review
Several neuroinvasive viruses can be used to study the mammalian nervous system. In particular, infection by pseudorabies virus (PRV), an alpha-herpesvirus with broad host range, reveals chains of functionally connected neurons in the nervous systems of a variety of mammals. The specificity of PRV trans-neuronal spread has been established in several systems. One attenuated strain, PRV-Bartha, causes a reduced inflammatory response and also spreads only from infected post- to pre-synaptic neurons. We review the basics of PRV tracing and then discuss new developments and novel approaches that have enabled a more detailed understanding of the architecture of the nervous system. As questions and techniques evolve in the field of neuroscience, advances in PRV tracing will certainly follow.
Topics: Alphaherpesvirinae; Animals; Green Fluorescent Proteins; Herpesvirus 1, Suid; Humans; Mice; Mice, Transgenic; Nervous System; Nervous System Physiological Phenomena; Neurobiology; Neurons
PubMed: 18280208
DOI: 10.1016/j.molmed.2007.12.008 -
Viruses Nov 2021Feline herpesvirus type 1 (FHV-1) is endemic in captive cheetahs and sporadically causes devastating disease. Modified live vaccines (MLV), intended for use in domestic...
Feline herpesvirus type 1 (FHV-1) is endemic in captive cheetahs and sporadically causes devastating disease. Modified live vaccines (MLV), intended for use in domestic cats, are used in some captive cheetah populations and have been anecdotally linked to disease in certain subpopulations. Ten FHV-1 isolates from ten captive cheetahs and one isolate from an MLV used to inoculate four of the host animals were analyzed. Viral DNA was extracted for full-genome sequencing by Illumina MiSeq with viral genomes then used for phylogenomic and recombinational analyses. The FHV-1 shed by vaccinated cheetahs were almost identical to the MLV, with few variants among viral genomes. Eight cheetah FHV-1 isolates and the MLV were grouped in a clade along with FHV-1 isolates from domestic cats in the USA. The remaining two cheetah FHV-1 isolates (unknown host vaccine status) were not associated with a clade. The likely ancestral origin of these two isolates involves recombination events between Australian domestic cat and cheetah FHV-1 isolates. Collectively, these data suggest that the MLV is capable of causing clinical disease and viral shedding in some cheetahs and represents evidence of interspecies transmission of virus between domestic and wild cats.
Topics: Acinonyx; Animals; Cat Diseases; Cats; Cell Line; Genome, Viral; Herpesviridae Infections; Vaccines, Attenuated; Varicellovirus
PubMed: 34835113
DOI: 10.3390/v13112307 -
Virology Journal Apr 2023Feline calicivirus (FCV) and feline herpesvirus type I (FHV-1) are the most common viral pathogens responsible for cat respiratory diseases, and coinfection with these...
Feline calicivirus (FCV) and feline herpesvirus type I (FHV-1) are the most common viral pathogens responsible for cat respiratory diseases, and coinfection with these two pathogens is often found. In veterinary clinics, the main diagnostic methods for FCV and FHV-1 are test strips and polymerase chain reaction (PCR). However, the sensitivity of test strips are not sufficient, and PCR is time-consuming. Therefore, developing a rapid and high-performance clinical diagnostic test is imperative for the prevention and treatment of these diseases. Enzymatic recombinase amplification (ERA) is an automated isothermal nucleic acid amplification technique that maintains a constant temperature, and is both rapid and highly accurate. In this study, a dual ERA method was developed using the Exo probe for a differential detection of FCV and FHV-1. This dual ERA method demonstrated high performance with the detection limit of 10 copies for both viruses, and no cross-reactions with feline parvovirus virus and F81 cells. To test the utility of the method for clinical applications, 50 nasopharyngeal swabs from cats with respiratory symptoms were collected and tested. The positive rates of FCV and FHV-1 were 40% (20/50, 95% confidence interval [CI], 26.4 to 54.8%) and 14% (7/50, 95% CI, 5.8 to 26.7%), respectively. The rate of coinfection with FCV and FHV-1 was 10% (5/50, 95% CI, 3.3 to 21.8%). These results were in agreement with those found using quantitative real-time PCR. Therefore, this dual ERA method is a novel and efficient clinical diagnostic tool for FCV and FHV-1 detection.
Topics: Cats; Animals; Calicivirus, Feline; Herpesviridae Infections; Recombinases; Coinfection; Varicellovirus; Real-Time Polymerase Chain Reaction; Cat Diseases; Caliciviridae Infections
PubMed: 37020252
DOI: 10.1186/s12985-023-02020-3 -
Microbiology Spectrum Jun 2022Superinfection exclusion (SIE) is a phenomenon in which a primary viral infection interferes with secondary viral infections within that same cell. Although SIE has been...
Superinfection exclusion (SIE) is a phenomenon in which a primary viral infection interferes with secondary viral infections within that same cell. Although SIE has been observed across many viruses, it has remained relatively understudied. A recently characterized glycoprotein D (gD)-independent SIE of alphaherpesviruses presents a novel mechanism of coinfection restriction for herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV). In this study, we evaluated the role of multiplicity of infection (MOI), receptor expression, and trafficking of virions to gain greater insight into potential mechanisms of alphaherpesvirus SIE. We observed that high-MOI secondary viral infections were able to overcome SIE in a manner that was independent of receptor availability. We next assessed virion localization during SIE through live microscopy of fluorescently labeled virions and capsid assemblies. Analysis of these fluorescent assemblies identified changes in the distribution of capsids during SIE. These results indicate that SIE during PRV infection inhibits viral entry or fusion while HSV-1 SIE inhibits infection through a postentry mechanism. Although the timing and phenotype of SIE are similar between alphaherpesviruses, the related viruses implement different mechanisms to restrict coinfection. Most viruses utilize a form of superinfection exclusion to conserve resources and control population dynamics. gD-dependent superinfection exclusion in alphaherpesviruses is well documented. However, the undercharacterized gD-independent SIE provides new insight into how alphaherpesviruses limit sequential infection. The observations described here demonstrate that gD-independent SIE differs between PRV and HSV-1. Comparing these differences provides new insights into the underlying mechanisms of SIE implemented by two related viruses.
Topics: Animals; Coinfection; Herpesvirus 1, Human; Herpesvirus 1, Suid; Superinfection; Virion
PubMed: 35604159
DOI: 10.1128/spectrum.00684-22 -
Nature Microbiology Dec 2020Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure...
Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.
Topics: Capsid; Capsid Proteins; Cryoelectron Microscopy; Herpesvirus 3, Human; Humans; Models, Molecular; Protein Domains; Varicella Zoster Virus Infection; Virion
PubMed: 32895526
DOI: 10.1038/s41564-020-0785-y -
Viruses Feb 2024The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV)...
The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the () gene of PRV or of the () and () of BHV-1. Upon the cleavage of the TK or gIgE gene by Cas9 protein, this was replaced by the () by homologous recombination. With this approach, we generated recombinant TK-/eGFP+ PRV and gIgE-/eGFP+ BHV-1 mutants and then proceeded to characterize their biological activities in vitro and in vivo. In conclusion, we showed that alpha herpesvirus, including PRV and BHV-1, can be rapidly edited using the CRISPR/Cas9 approach paving the way to the development of animal herpesvirus vaccines.
Topics: Animals; Herpesvirus 1, Suid; Gene Editing; CRISPR-Cas Systems; Herpesvirus 1, Bovine; Pseudorabies; Glycoproteins
PubMed: 38400086
DOI: 10.3390/v16020311 -
Viruses Jul 2021Caprine herpesvirus 1 (CpHV-1) is a member of the alpha subfamily of herpesviruses, which is responsible for genital lesions and latent infections in goat populations...
Caprine herpesvirus 1 (CpHV-1) is a member of the alpha subfamily of herpesviruses, which is responsible for genital lesions and latent infections in goat populations worldwide. In this study, for the first time, the transcriptome and proteomics of CpHV-1 infected Madin Darby bovine kidney (MDBK) cells were explored using RNA-Sequencing (RNA-Seq) and isobaric tags for relative and absolute quantitation-liquid chromatography tandem mass spectrometry (iTRAQ-LC-MS/MS) technology, respectively. RNA-Seq analysis revealed 81 up-regulated and 19 down-regulated differentially expressed genes (DEGs) between infected and mock-infected MDBK cells. Bioinformatics analysis revealed that most of these DEGs were mainly involved in the innate immune response, especially the interferon stimulated genes (ISGs). Gene Ontology (GO) enrichment analysis results indicated that the identified DEGs were significantly mainly enriched for response to virus, defense response to virus, response to biotic stimulus and regulation of innate immune response. Viral carcinogenesis, the RIG-I-like receptor signaling pathway, the cytosolic DNA-sensing pathway and pathways associated with several viral infections were found to be significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Eleven selected DEGs (Mx1, RSAD2, IFIT1, IFIT2, IFIT5, IFIH1, IFITM3, IRF7, IRF9, OAS1X and OAS1Y) associated with immune responses were selected, and they exhibited a concordant direction both in RNA-Seq and quantitative real-time RT-PCR analysis. Proteomic analysis also showed significant up-regulation of innate immunity-related proteins. GO analysis showed that the differentially expressed proteins were mostly enriched in defense response and response to virus, and the pathways associated with viral infection were enriched under KEGG analysis. Protein-protein interaction network analysis indicated most of the DEGs related to innate immune responses, as DDX58(RIG-I), IFIH1(MDA5), IRF7, Mx1, RSAD2, OAS1 and IFIT1, were located in the core of the network and highly connected with other DGEs. Our findings support the notion that CpHV-1 infection induced the transcription and protein expression alterations of a series of genes related to host innate immune response, which helps to elucidate the resistance of host cells to viral infection and to clarify the pathogenesis of CpHV-1.
Topics: Animals; Cattle; Cell Line; Chromatography, Liquid; Computational Biology; Gene Expression Profiling; Hepatocytes; Immunity, Innate; Kidney; Proteomics; Sequence Analysis, RNA; Tandem Mass Spectrometry; Transcriptome; Up-Regulation; Varicellovirus; Virus Replication
PubMed: 34372499
DOI: 10.3390/v13071293 -
British Medical Journal Oct 1956
Topics: Herpes Zoster; Herpesvirus 3, Human; Humans; Medical Records
PubMed: 13364347
DOI: 10.1136/bmj.2.4997.864 -
Microbiology and Molecular Biology... Sep 2023Varicella-zoster virus (VZV) is a human alphaherpesvirus that causes varicella (chicken pox) as the primary infection in a susceptible host. Varicella is very contagious... (Review)
Review
Varicella-zoster virus (VZV) is a human alphaherpesvirus that causes varicella (chicken pox) as the primary infection in a susceptible host. Varicella is very contagious through its transmission by direct contact with vesicular skin lesions that contain high titers of infectious virus and respiratory droplets. While the clinical manifestations of primary VZV infection are well recognized, defining the molecular mechanisms that drive VZV pathogenesis in the naive host before adaptive antiviral immunity is induced has been a challenge due to species specificity. This review focuses on advances made in identifying the differentiated human host cells targeted by VZV to cause varicella, the processes involved in viral takeover of these heterogenous cell types, and the host cell countermeasures that typically culminate in a benign illness. This work has revealed many unexpected and multifaceted mechanisms used by VZV to achieve its high prevalence and persistence in the human population.
Topics: Humans; Herpesvirus 3, Human; Chickenpox; Antiviral Agents
PubMed: 37354037
DOI: 10.1128/mmbr.00116-22 -
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