Bovine herpesvirus 1 downregulates the expression of bovine MHC class I molecules.
The mechanism of immunosuppression induced by bovine herpesvirus 1 (BHV-1) was investigated by studying the effects of the virus on the expression of major histocompatibility complex (MHC) class I molecules. After infection with the virus, the expression of class I molecules was detected by flow cytometry and pulse-chase analysis. A selective downregulation of expression of class I molecules was seen in the infected cells, while the class II expression remained unaffected. The reduction in surface expression was evident as early as 8 hours postinfection, reaching significant levels by 12 hours. The downregulation was seen with a multiplicity of infection as low as 0.1. A modified live vaccine strain of BHV-1 also induced the downregulation of class I expression. Analysis of the viral proteins(s) involved in this downregulation with metabolic inhibitors (cycloheximide or phosphonoacetic acid), suggested that the immediate early and/or early proteins of the virus mediate this effect. Pulse-chase analysis revealed that the synthesis of the class I heavy chain, and the assembly/transport of class I molecules were affected by the virus infection. These results suggest that BHV-1 interferes with the molecular mechanisms involved in the synthesis, and assembly/transport of MHC-class I molecules. This interference with the class I antigen processing pathway might help the virus to evade the cytotoxic T-lymphocyte response of the host.
Nataraj
C
C
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, USA.
Eidmann
S
S
Hariharan
M J
MJ
Sur
J H
JH
Perry
G A
GA
Srikumaran
S
S
D000818:Animals; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D004594:Electrophysiology; D015967:Gene Expression Regulation, Viral; D005805:Genes, MHC Class I; D018869:Heat-Shock Response; D007242:Herpesvirus 1, Bovine / Q000276:immunology*; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D011500:Protein Synthesis Inhibitors; D014764:Viral Proteins; D003513:Cycloheximide; D010746:Phosphonoacetic Acid