HUMAN CYTOMEGALOVIRUS INHIBITS ANTIGEN PRESENTATION BY A SEQUENTIAL MULTISTEP PROCESS

The human cytomegalovirus (HCMV) genomic unique short (US) region enco des a family of homologous genes essential for the inhibition of major histocompatibility complex (MHC) class I-mediated antigen presentatio n during viral infection, Here we show that US3, the only immediate ea rly (IE) gene within the US region, encodes an endoplasmic reticulum-r esident glycoprotein that prevents intracellular transport of MHC clas s I molecules, in contrast to the rapid degradation of newly synthesiz ed MHC class I heavy chains mediated by the early gene product US11, w e found that US3 retains stable MHC class I heterodimers in the endopl asmic reticulum that are loaded with peptides while retained in the ER , Consistent with the expression pattern of US3 and US11, MHC class I molecules are retained but not degraded during the IE period of infect ion. Our data identify the first nonregulatory role of an IE protein o f HCMV and suggest that HCMV uses different T-cell escape strategies a t different times during the infectious cycle.