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Lack of virulence of the murine fibroblast adapted strain, Kentucky A (KyA), of equine herpesvirus type 1 (EHV-1) in young horses.
Abstract: The virulence of the cell culture adapted KyA strain of equine herpesvirus type 1 (EHV-1), which lacks at least six genes by deletions in its genome, was assessed by intranasal inoculation of six young horses that were serologically negative for EHV-1. No horses showed clinical signs, and a neutralizing antibody response against EHV-1 was detected in two horses which had antibodies against EHV-4 prior to the inoculation. A challenge experiment using a highly virulent strain of EHV-1 conducted 4 weeks later against 4 of the 6 horses inoculated intranasally with the KyA strain and 2 control horses revealed that (i) the KyA inoculated horses were protected from manifestation of clinical signs detected in both control horses, with the exception of pyrexia, (ii) duration of virus isolation from the KyA inoculated horses after the challenge was remarkably shortened as compared to that from control horses; (iii) thus, animals inoculated with the KyA and challenged with pathogenic EHV-1 showed a reduction in the time of virus shedding and viremia; (iv) two horses which exhibited no antibody responses after the KyA inoculation showed antibody responses after the challenge significantly higher than those of control horses. The results reveal that the KyA strain has no virulence but still possesses immunogenicity for horses, suggesting that some of the genes deleted from the KyA strain might have importance in the expression of EHV-1 virulence.
Publication Date: 1996-02-01 PubMed ID: 9054131DOI: 10.1016/0378-1135(09)59999-3Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The study investigated the virulence of the Kentucky A (KyA) strain of equine herpesvirus type 1 (EHV-1), which is adapted to murine fibroblasts and has six genes deleted from its genome, in young horses. Results showed that the strain is not virulent but has immunogenic properties, hinting that the deleted genes might have been crucial to the virus’ pathogenic power.
Explaining the Methods and Subjects
- The study involved the use of the KyA strain of EHV-1, which has adapted to cell cultures and has at least six genes deleted from its genome. This strain was used to inoculate six young horses intranasally.
- The horses used in this study were already serologically negative for EHV-1, which means they did not previously have antibodies against this virus, making them suitable subjects to test the virulence and immunogenic properties of the KyA strain.
Observations Made
- None of the horses showed any clinical signs of disease after being inoculated with the KyA strain, indicating the absence of virulence in this strain.
- Only two horses developed a neutralizing antibody response against EHV-1, and these horses had antibodies against EHV-4 prior to the inoculation, suggesting some form of immunogenic cross-reactivity between the two herpesvirus types.
Challenge Experiment
- Four weeks after the inoculation, a challenge experiment was conducted using a highly virulent strain of EHV-1. This was tested on four of the initial KyA-inoculated horses and two control horses.
- The results revealed that the initially inoculated horses were protected from clinical signs that were observed in the control group, with the exception of pyrexia (fever), indicating the protective immunogenic effect exerted by the KyA strain.
Reduced Virus Isolation and Shedding
- There was also a considerable reduction in the duration of virus isolation from the KyA-inoculated horses following the challenge, indicating a decrease in the time of virus shedding and viremia (presence of the virus in the blood).
- Two of the horses which did not exhibit any antibody responses after the initial inoculation developed significant antibody responses after the challenge – effectively higher than those seen in control horses.
Findings and Suggestions
- All these observations collectively reveal the KyA strain’s lack of virulence but ongoing capability for inducing immune responses in horses.
- This hints that the genes deleted from the KyA strain could have had potential roles in EHV-1’s expression of virulence, providing an important piece of knowledge for understanding this virus and devising control strategies against it.
Cite This Article
APA
Matsumura T, O'Callaghan DJ, Kondo T, Kamada M.
(1996).
Lack of virulence of the murine fibroblast adapted strain, Kentucky A (KyA), of equine herpesvirus type 1 (EHV-1) in young horses.
Vet Microbiol, 48(3-4), 353-365.
https://doi.org/10.1016/0378-1135(09)59999-3 Publication
Researcher Affiliations
- Epizootic Research Station, Equine Research Institute, Japan Racing Association, Tochigi, Japan.
MeSH Terms
- Animals
- Antibodies, Viral / biosynthesis
- Antibodies, Viral / blood
- Antibody Formation
- Cattle
- Cell Line
- DNA, Viral / isolation & purification
- Gene Deletion
- Herpesviridae Infections / immunology
- Herpesviridae Infections / physiopathology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / pathogenicity
- Horse Diseases / virology
- Horses
- L Cells
- Mice
- Molecular Sequence Data
- Neutralization Tests
- Viremia / immunology
- Viremia / physiopathology
- Viremia / veterinary
- Virulence / genetics
Grant Funding
- AI-22001 / NIAID NIH HHS
Citations
This article has been cited 14 times.- Kim SK, Shakya AK, O'Callaghan DJ. Interferon Gamma Inhibits Equine Herpesvirus 1 Replication in a Cell Line-Dependent Manner. Pathogens 2021 Apr 16;10(4).
- 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).
- Kim SK, Shakya AK, O'Callaghan DJ. Intranasal treatment with CpG-B oligodeoxynucleotides protects CBA mice from lethal equine herpesvirus 1 challenge by an innate immune response. Antiviral Res 2019 Sep;169:104546.
- 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.
- Lewin AC, Kolb AW, McLellan GJ, Bentley E, Bernard KA, Newbury SP, Brandt CR. Genomic, Recombinational and Phylogenetic Characterization of Global Feline Herpesvirus 1 Isolates. Virology 2018 May;518:385-397.
- 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.
- Charvat RA, Breitenbach JE, Ahn B, Zhang Y, O'Callaghan DJ. The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters. Virology 2011 Apr 10;412(2):366-77.
- 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.
- 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.
- Bowles DE, Holden VR, Zhao Y, O'Callaghan DJ. The ICP0 protein of equine herpesvirus 1 is an early protein that independently transactivates expression of all classes of viral promoters. J Virol 1997 Jul;71(7):4904-14.
- 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.
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