Down-regulation of MHC class I expression by equine herpesvirus-1.
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.
Rappocciolo
Giovanna
G
Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
Birch
James
J
Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
Ellis
Shirley A
SA
Department of Immunology and Pathology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
D000483:Alleles; D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005805:Genes, MHC Class I; D004861:Herpesvirus 1, Equid / Q000187:drug effects / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D004791:Enzyme Inhibitors; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D010746:Phosphonoacetic Acid