Human cytomegalovirus down-regulates HLA class I expression by reducing the stability of class I H chains.
Human CMV (HCMV) infection leads to an almost complete inhibition of expression of MHC class I proteins. After infection with HCMV, the biosynthesis of HLA class I molecules was examined in human lung fibroblasts and in mouse fibroblasts transfected with genes encoding the human class I H chain HLA-B27 and human beta 2-microglobulin (beta 2m). In both cell types, we observed a large decrease in steady state levels specific for human class I H chains--both free H chains and those complexed with beta 2m. In the mouse cells transfected with HLA class I, infection did not affect levels and assembly of mouse class I H chains with human beta 2m. The effect of HCMV infection on class I expression is insensitive to phosphonoacetic acid, suggesting the involvement of immediate early or early viral proteins. Pulse-chase analysis showed that the low steady state level of class I H chains in HCMV-infected cells is not the result of a reduced rate of synthesis. Rather, we observed accelerated degradation of class I H chains, regardless of their association with beta 2m. We conclude that HCMV reduces human MHC class I protein levels by interference with the stability of class I H chains.
Beersma
M F
MF
Department of Ophthalmo-immunology, The Netherlands Ophthalmic Research Institute, Amsterdam.
Bijlmakers
M J
MJ
Ploegh
H L
HL
D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity*; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D051379:Mice; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis; D001613:beta 2-Microglobulin / Q000032:analysis
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; D001613:beta 2-Microglobulin