Down-regulation of MHC class I expression by equine herpesvirus-1.
Abstract: There is good evidence that cytotoxic T lymphocytes play an important role in the clearance of equine herpesvirus-1 (EHV1) in horses. We have demonstrated that, in common with other alphaherpesviruses, EHV1 infection can lead to dramatic down-regulation of MHC class I expression at the cell surface, a common strategy for pathogen evasion of the host immune response. This down-regulation is specific for MHC class I and does not reflect a general shut-off of host-cell protein synthesis. The use of monoclonal antibodies that recognize different MHC class I epitopes has demonstrated that the effect may be allele- or locus-specific. Use of the viral DNA synthesis inhibitor phosphonoacetic acid, which prevents late viral gene expression, showed that the effect is mediated by an immediate-early or early viral gene, and use of the protein translation inhibitor cycloheximide confirmed that an early gene is primarily responsible. The data indicate that EHV1 infection results in enhanced endocytosis of MHC class I from the cell surface; the only other herpesvirus reported to use this mechanism is human herpesvirus-8. Elucidation of the precise mechanisms used by EHV1 in this process and identification of the genes responsible may lead to improved vaccination strategies.
Publication Date: 2003-02-01 PubMed ID: 12560560DOI: 10.1099/vir.0.18612-0Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study has provided evidence that equine herpesvirus-1 (EHV1) infection in horses causes a significant reduction in MHC class I expression on the surface of infected cells, a strategy employed by the pathogen to escape the host’s immune response.
Key Findings
- EHV1 infection in horses leads to a substantial down-regulation of MHC class I molecules on the cell surface. This is a usual tactic that the pathogen employs to evade host immunity. This effect is, however, specific to MHC class I and does not denote a total shutdown of host-cell protein synthesis.
- An analysis carried out using monoclonal antibodies found that the down-regulation effect may be allele- or locus-specific.
- The use of phosphonoacetic acid, a viral DNA synthesis inhibitor, established that an immediate-early or early viral gene mediates this process. The employment of cycloheximide, a protein translation inhibitor, reconfirmed that it is the early gene that bears primary responsibility.
- The study found that EHV1 infection accelerates the endocytosis of MHC class I from the cell surface. Interestingly, human herpesvirus-8 is the only other known herpesvirus to use this approach.
Implications and Conclusion
- Understanding these mechanisms employed by EHV1 will greatly implicate potential targets for drugs and vaccines. Pinpointing the genes responsible for this process can lead to the development of improved vaccination strategies against EHV1.
- Comparative studies between EHV1 and other herpesviruses, especially human herpesvirus-8, could also lead to further discoveries relevant to the field.
Cite This Article
APA
Rappocciolo G, Birch J, Ellis SA.
(2003).
Down-regulation of MHC class I expression by equine herpesvirus-1.
J Gen Virol, 84(Pt 2), 293-300.
https://doi.org/10.1099/vir.0.18612-0 Publication
Researcher Affiliations
- Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
- Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
- Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
MeSH Terms
- Alleles
- Animals
- Cell Line
- Cycloheximide / pharmacology
- Down-Regulation
- Enzyme Inhibitors / pharmacology
- Genes, MHC Class I
- Herpesvirus 1, Equid / drug effects
- Herpesvirus 1, Equid / pathogenicity
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / metabolism
- Immediate-Early Proteins / genetics
- Immediate-Early Proteins / metabolism
- Phosphonoacetic Acid / pharmacology
- Protein Synthesis Inhibitors / pharmacology
Citations
This article has been cited 14 times.- Tsai MS, François S, Newman C, Macdonald DW, Buesching CD. Infection with a Recently Discovered Gammaherpesvirus Variant in European Badgers, Meles meles, is Associated with Higher Relative Viral Loads in Blood.. Pathogens 2022 Oct 6;11(10).
- Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.. Front Vet Sci 2021;8:674850.
- Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, Azab W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs.. Viruses 2020 Sep 8;12(9).
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- Said A, Azab W, Damiani A, Osterrieder N. Equine herpesvirus type 4 UL56 and UL49.5 proteins downregulate cell surface major histocompatibility complex class I expression independently of each other.. J Virol 2012 Aug;86(15):8059-71.
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