Effects of virion host shut-off activity of bovine herpesvirus 1 on MHC class I expression.
Previously, we have shown that bovine herpesvirus 1 (BHV-1) down-regulates the expression of major histocompatibility complex class I molecules by interfering with transport of peptides by the transporter associated with antigen processing (TAP). Further studies revealed that BHV-1 down-regulates the expression of mRNA for class I molecules and other cellular proteins. To further elucidate the mechanisms of down-regulation of class I molecules, a virion host shut-off (vhs) deletion mutant was generated. The mutant, like the wildtype (wt) virus, interfered with transport of peptides by the TAP, and down-regulated cell surface expression of class I molecules. However, unlike the wt virus, the mutant did not impair the synthesis of class I molecules. These results indicate that down-regulation of class I molecules by BHV-1 is mediated by vhs activity of the virus, as well as mechanisms specifically directed at the class I pathway. Absence of vhs activity should result in decreased pathogenicity and enhanced immunogenicity of BHV-1 vhs deletion mutant, making it a better vaccine candidate.
Gopinath
R S
RS
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska 68583-0905, USA.
Ambagala
A P N
AP
Hinkley
S
S
Srikumaran
S
S
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D015536:Down-Regulation; D005805:Genes, MHC Class I; D007242:Herpesvirus 1, Bovine / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D012260:Ribonucleases; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases