An equine herpesvirus type 1 recombinant with a deletion in the gE and gI genes is avirulent in young horses.
Abstract: The cell culture-adapted KyA strain of equine herpesvirus type 1 (EHV-1) has been found to be attenuated in young horses (Matsumura et al., 1996, Vet. Microbiol. 48, 353-365). The KyA strain lacks at least six genes in its genome, including those encoding glycoproteins gE and gI. To elucidate whether EHV-1 glycoproteins gE and gI play a role in viral virulence, we have constructed an EHV-1 recombinant that has the genes encoding both gE and gI deleted from its genome and its revertant. Growth properties of the deletion mutant virus in vitro were compared with those of the parent and the revertant viruses. Plaque size of the mutant virus in fetal horse kidney (FHK) cells was significantly smaller than those of the parent and the revertant viruses. In one-step growth experiments, however, the yields of infectious virus from FHK cells infected with the deletion mutant, the parent, or the revertant virus were approximately the same. The results suggested that gE and/or gI of EHV-1 promoted cell-to-cell spread of the virus, but that these glycoproteins were not involved in the process of virus maturation and release or in virus attachment and penetration. Subsequently, the virulence of mutant and revertant viruses was examined in young horses. No clinical signs were observed in six horses, including three colostrum-deprived foals inoculated intranasally with the deletion mutant virus, whereas three colostrum-deprived foals inoculated intranasally with the revertant virus manifested clinical signs typical for EHV-1 respiratory infection (i.e., pyrexia, nasal discharge, and swelling of submandibular lymph nodes). The results obtained from in vivo studies revealed that the EHV-1 mutant defective in both gE and gI genes was avirulent in young horses, suggesting that gE and/or gI of the EHV-1 have an important role in EHV-1 virulence. However, the EHV-1 mutant defective in both gE and gI genes induced only a partial protectivity in inoculated foals from manifestation of respiratory symptoms after challenge infection.
Publication Date: 1998-03-17 PubMed ID: 9501037DOI: 10.1006/viro.1997.8984Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research investigates the role of two genes, gE and gI, in the virulence of equine herpesvirus type 1 (EHV-1) in young horses. It found that an EHV-1 strain missing these genes was avirulent, meaning it did not cause disease in the horses tested, suggesting these genes play a key role in the virus’s virulence.
Background and Methods
- Previously, a strain of EHV-1, called the KyA strain, was found to be attenuated, or less virulent, in young horses. The genome of this strain was missing at least six genes, including those coding for glycoproteins gE and gI.
- To investigate if these glycoproteins played a role in the virus’s capability to cause disease, or virulence, the authors created an EHV-1 recombinant. This is a strain of the virus where specific genes are deleted or inserted. In this case, the gE and gI genes were deleted.
Lab Experiments
- The growth of this recombinant virus was compared to that of the original strain and of a “revertant” virus, where the gE and gI genes were re-inserted. The size of the plaques, or areas of cell death, caused by the mutant virus were significantly smaller in cultures of horse kidney cells.
- However, the productivity of the virus – the number of new viruses produced by infected cells – was similar across all three strains. This suggested to the researchers that the gE and gI genes weren’t involved in the virus’s ability to mature and release from the cell, or to initially attach and penetrate the cell, but rather in its ability to spread from one cell to another.
In vivo Studies
- The researchers then examined the virulence of the recombinant and revertant viruses in young horses. Intranasal inoculation of the recombinant virus did not cause any symptoms in six horses, while those infected with the revertant virus showed typical signs of EHV-1 respiratory infection. This confirms that the mutant EHV-1 strain missing gE and gI genes did not cause disease in young horses, hence was avirulent.
- In contrast, horses inoculated with the revertant (original) virus exhibited typical clinical signs of EHV-1 respiratory infections such as fever, nasal discharge, and swollen lymph nodes.
- Therefore, this study revealed that the absence of gE and gI causes EHV-1 to become avirulent in horses, meaning these genes are crucial for EHV-1’s virulence.
- However, the mutant EHV-1 only provided partial protection to the inoculated horses from respiratory symptoms after challenge infection, suggesting that it might not result in strong immunity towards the virus.
Cite This Article
APA
Matsumura T, Kondo T, Sugita S, Damiani AM, O'Callaghan DJ, Imagawa H.
(1998).
An equine herpesvirus type 1 recombinant with a deletion in the gE and gI genes is avirulent in young horses.
Virology, 242(1), 68-79.
https://doi.org/10.1006/viro.1997.8984 Publication
Researcher Affiliations
- Epizootic Research Station, Equine Research Institute, Japan Racing Association, Tochigi, Japan. tomats@epizoo.equinst.go.jp
MeSH Terms
- Animals
- Cells, Cultured
- Fetus
- Gene Deletion
- Herpesviridae Infections / physiopathology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / pathogenicity
- Herpesvirus 1, Equid / physiology
- Horse Diseases
- Horses
- Kidney / virology
- Polymerase Chain Reaction
- Recombination, Genetic
- Restriction Mapping
- Viral Envelope Proteins / biosynthesis
- Viral Envelope Proteins / genetics
- Viral Plaque Assay
- Virulence
- Virus Replication
Grant Funding
- AI-22001 / NIAID NIH HHS
Citations
This article has been cited 17 times.- Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G. Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses. Viruses 2021 Feb 24;13(3).
- Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection. Pathogens 2021 Jan 7;10(1).
- Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease. J Virol 2019 Nov 15;93(22).
- Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A, Wagner B. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. PLoS One 2018;13(11):e0206679.
- Shakya AK, O'Callaghan DJ, Kim SK. Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11. Front Vet Sci 2017;4:211.
- Kim SK, Shakya AK, O'Callaghan DJ. Immunization with Attenuated Equine Herpesvirus 1 Strain KyA Induces Innate Immune Responses That Protect Mice from Lethal Challenge. J Virol 2016 Sep 15;90(18):8090-104.
- Andoh K, Kai K, Matsumura T, Maeda K. Further Development of an Equine Cell Line that can be Propagated over 100 Times. J Equine Sci 2009;20(2):11-4.
- Frampton AR Jr, Smith PM, Zhang Y, Grafton WD, Matsumura T, Osterrieder N, O'Callaghan DJ. Meningoencephalitis in mice infected with an equine herpesvirus 1 strain KyA recombinant expressing glycoprotein I and glycoprotein E. Virus Genes 2004 Aug;29(1):9-17.
- von Einem J, Wellington J, Whalley JM, Osterrieder K, O'Callaghan DJ, Osterrieder N. The truncated form of glycoprotein gp2 of equine herpesvirus 1 (EHV-1) vaccine strain KyA is not functionally equivalent to full-length gp2 encoded by EHV-1 wild-type strain RacL11. J Virol 2004 Mar;78(6):3003-13.
- Rizvi SM, Raghavan M. Responses of herpes simplex virus type 1-infected cells to the presence of extracellular antibodies: gE-dependent glycoprotein capping and enhancement in cell-to-cell spread. J Virol 2003 Jan;77(1):701-8.
- Rudolph J, Seyboldt C, Granzow H, Osterrieder N. The gene 10 (UL49.5) product of equine herpesvirus 1 is necessary and sufficient for functional processing of glycoprotein M. J Virol 2002 Mar;76(6):2952-63.
- Smith PM, Zhang Y, Grafton WD, Jennings SR, O'Callaghan DJ. Severe murine lung immunopathology elicited by the pathogenic equine herpesvirus 1 strain RacL11 correlates with early production of macrophage inflammatory proteins 1alpha, 1beta, and 2 and tumor necrosis factor alpha. J Virol 2000 Nov;74(21):10034-40.
- Smith PM, Zhang Y, Jennings SR, O'Callaghan DJ. Characterization of the cytolytic T-lymphocyte response to a candidate vaccine strain of equine herpesvirus 1 in CBA mice. J Virol 1998 Jul;72(7):5366-72.
- Kasem S, Abdel-Moneim AS, Fukushi H. Effect of thymidine kinase-deficiency (∆ORF38) on neuropathogenicity of equine herpesvirus-1 in the mouse model and expression of neighboring genes. Virus Genes 2025 Apr;61(2):179-192.
- Nayel M, Kasem S, Fukushi N, El-Habashi N, Elsify A, Salama A, Hassan H, Yanai T, Ohya K, Fukushi H. Equine Herpesvirus Type 1 ORF76 Encoding US9 as a Neurovirulence Factor in the Mouse Infection Model. Pathogens 2024 Oct 2;13(10).
- Nishimura F, Fukushi N, Sakai H, Fukushi H. Attenuation of the neuropathogenic equine herpesvirus type 1 strain Ab4p in hamsters by a single amino acid mutation (D752N) in viral DNA polymerase ORF30. J Vet Med Sci 2024 Dec 1;86(12):1273-1278.
- Hassanien RT, Thieulent CJ, Carossino M, Li G, Balasuriya UBR. Modulation of Equid Herpesvirus-1 Replication Dynamics In Vitro Using CRISPR/Cas9-Assisted Genome Editing. Viruses 2024 Mar 6;16(3).
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