Human cytomegalovirus inhibits antigen presentation by a sequential multistep process.
The human cytomegalovirus (HCMV) genomic unique short (US) region encodes a family of homologous genes essential for the inhibition of major histocompatibility complex (MHC) class I-mediated antigen presentation during viral infection. Here we show that US3, the only immediate early (IE) gene within the US region, encodes an endoplasmic reticulum-resident glycoprotein that prevents intracellular transport of MHC class I molecules. In contrast to the rapid degradation of newly synthesized MHC class I heavy chains mediated by the early gene product US11, we found that US3 retains stable MHC class I heterodimers in the endoplasmic 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 infection. Our data identify the first nonregulatory role of an IE protein of HCMV and suggest that HCMV uses different T-cell escape strategies at different times during the infectious cycle.
Ahn
K
K
R. W. Johnson Pharmaceutical Research Institute, La Jolla, CA, USA.
Angulo
A
A
Ghazal
P
P
Peterson
P A
PA
Yang
Y
Y
Früh
K
K
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017781:Genes, Immediate-Early; D005814:Genes, Viral; D006023:Glycoproteins / Q000737:chemistry; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000276:immunology; D015678:Viral Structural Proteins / Q000235:genetics
D000956:Antigens, Viral; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D010455:Peptides; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C095111:US3 protein, cytomegalovirus; D014764:Viral Proteins; D015678:Viral Structural Proteins