IDENTIFICATION OF HUMAN CYTOMEGALOVIRUS GENES INVOLVED IN DOWN-REGULATION OF MHC CLASS I HEAVY CHAIN EXPRESSION

摘要

The human cytomegalovirus (HCMV) genomic US region encodes a family of homologous genes essential for the inhibition of major histocompatibility complex (MHC) class I mediated antigen presentation observed during viral infection. Here we show that US3 and US6 encode ER-resident glycoproteins that prevent intracellular transport of MHC class I molecules by different mechanisms. US3 retains stable MHC class I heterodimers in the ER which are loaded with peptides while retained in the ER. US6 prevents MHC class I assembly with β2 microglobulin which results in free heavy chains leaving the ER. These genes have the potential to prevent unwanted immunological reactivities triggered by MHC class I molecules.