A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1.
Abstract: Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds with characterized MHC class I haplotypes and screened against P815 target cells transfected with selected EHV-1 genes and MHC class I genes. Targets that expressed EHV-1 gene 64 and the MHC B2 gene were lysed by effector CTL in a genetically restricted manner. There was no T-cell recognition of targets expressing either the MHC B2 gene and EHV-1 genes 2, 12, 14, 16, 35, 63 or 69, or the MHC C1 gene and EHV-1 genes 12, 14, 16 or 64. A vaccinia virus vector encoding gene 64 (NYVAC-64) was also investigated. Using lymphocytes from ELA-A3 horses, the recombinant NYVAC-64 virus induced effector CTL that lysed EHV-1-infected target cells; the recombinant virus also supplied a functional peptide that was expressed by target cells and recognized in an MHC-restricted fashion by CTL induced with EHV-1. This construct may therefore be used to determine the antigenicity of EHV-1 gene 64 for other MHC haplotypes. These techniques are broadly applicable to the identification of additional CTL target proteins and their presenting MHC alleles, not only for EHV-1, but for other equine viruses.
Publication Date: 2006-08-09 PubMed ID: 16894188DOI: 10.1099/vir.0.82070-0Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses a study that aimed to identify cytotoxic T lymphocytes (CTL) epitopes within the equine herpesvirus 1 (EHV-1) that may be responsible for causing diseases in horses, including respiratory and neurological diseases, and abortion.
Introduction
- The focus of this study is on equine herpesvirus 1 (EHV-1), a virus causing respiratory and neurological disease and abortion in horses.
- It has been observed that horses with a higher frequency of cells called cytotoxic T lymphocytes (CTL) have less severe respiratory disease and fewer instances of abortion. This indicates that CTLs may be crucial in controlling the severity of the virus.
Objective
- The researchers wanted to understand more about how these CTLs work in reducing the severity of the disease and, thus, aimed to identify the specific sections (epitopes) of the CTLs that interact with EHV-1.
- This identification could potentially lead to a better understanding of virus control and even the development of more effective vaccines.
Method
- CTLs were induced from EHV-1-infected thoroughbreds and ponies with specific major histocompatibility complex (MHC) class I alleles associated with the equine leukocyte antigen (ELA) A3 haplotype. These CTLs were then screened against target cells transfected (genetically modified) with selected EHV-1 genes and MHC class I genes.
- Additionally, a vaccinia virus vector encoding gene 64 (NYVAC-64) was used for investigation. This method allowed the researchers to assess CTL reaction towards EHV-1 gene 64.
Results
- The findings show that target cells expressing the EHV-1 gene 64 and the MHC B2 gene were destroyed by CTLs in a genetically restricted manner. However, there was no recognition from the T-cell targets expressing different combinations of MHC B2 gene, MHC C1 gene and EHV-1 genes.
- Through the use of the NYVAC-64 vector, it was also discovered that this construct could induce CTLs that effectively destroyed EHV-1-infected target cells. Interestingly, this recombinant virus also produced a functional peptide (a short chain of amino acids crucial for cell functioning) that was recognized by CTLs induced by EHV-1 in an MHC-restricted manner.
Conclusion
- The results indicate that the techniques used within this study could be applied more broadly to the identification of additional CTL target proteins and their presenting MHC alleles, not only for EHV-1, but for other equine viruses too.
- Improving the understanding of CTLs and their interaction with viruses can potentially enhance the control and prevention methods of serious equine diseases.
Cite This Article
APA
Kydd JH, Davis-Poynter NJ, Birch J, Hannant D, Minke J, Audonnet JC, Antczak DF, Ellis SA.
(2006).
A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1.
J Gen Virol, 87(Pt 9), 2507-2515.
https://doi.org/10.1099/vir.0.82070-0 Publication
Researcher Affiliations
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.
- Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.
- Merial SAS, 254 rue Marcel Mérieux, 69007 Lyon, France.
- Merial SAS, 254 rue Marcel Mérieux, 69007 Lyon, France.
- James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
- Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
MeSH Terms
- Alleles
- Animals
- Antigens, Viral / genetics
- Base Sequence
- Cloning, Molecular
- DNA, Viral / genetics
- Epitopes / genetics
- Genes, MHC Class I
- Genes, Viral
- Genetic Vectors
- Herpesviridae Infections / genetics
- Herpesviridae Infections / immunology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Herpesvirus 1, Equid / genetics
- Herpesvirus 1, Equid / immunology
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horse Diseases / virology
- Horses
- In Vitro Techniques
- T-Lymphocytes, Cytotoxic / immunology
- Transfection
- Vaccinia virus / genetics
- Vaccinia virus / immunology
Citations
This article has been cited 4 times.- Oladunni FS, Horohov DW, Chambers TM. EHV-1: A Constant Threat to the Horse Industry. Front Microbiol 2019;10:2668.
- Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF, Sette A. The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires. Immunogenetics 2015 Nov;67(11-12):675-89.
- Guzman E, Taylor G, Charleston B, Ellis SA. Induction of a cross-reactive CD8(+) T cell response following foot-and-mouth disease virus vaccination. J Virol 2010 Dec;84(23):12375-84.
- Tallmadge RL, Campbell JA, Miller DC, Antczak DF. Analysis of MHC class I genes across horse MHC haplotypes. Immunogenetics 2010 Mar;62(3):159-72.
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