Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains.
The human cytomegalovirus (HCMV) early glycoprotein products of the US11 and US2 open reading frames cause increased turnover of major histocompatibility complex (MHC) class I heavy chains. Since US2 is homologous to another HCMV gene (US3), we hypothesized that the US3 gene product also may affect MHC class I expression. In cells constitutively expressing the HCMV US3 gene, MHC class I heavy chains formed a stable complex with beta 2-microglobulin. However, maturation of the N-linked glycan of MHC class I heavy chains was impaired in US3+ cells. The glycoprotein product of US3 (gpUS3) occurs mostly in a high-mannose form and coimmunoprecipitates with beta 2-microglobulin associated class I heavy chains. Mature class I molecules were detected at steady state on the surface of US3+ cells, as in control cells. Substantial perinuclear accumulation of heavy chains was observed in US3+ cells. The data suggest that gpUS3 impairs egress of MHC class I heavy chains from the endoplasmic reticulum.
Jones
T R
TR
Department of Molecular Biology, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. jonest@war.wyeth.com
Wiertz
E J
EJ
Sun
L
L
Fish
K N
KN
Nelson
J A
JA
Ploegh
H L
HL
D000911:Antibodies, Monoclonal; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004279:DNA, Viral; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D005982:Glutathione Transferase; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000302:isolation & purification / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; C095111:US3 protein, cytomegalovirus; D001613:beta 2-Microglobulin; D005982:Glutathione Transferase