Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains

Thomas R. Jones, Emmanuel J.H.J. Wiertz, Lei Sun, Kenneth N. Fish, Jay A. Nelson, Hidde L. Ploegh

Research output: Contribution to journalArticle

326 Scopus citations

Abstract

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 β2-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 β2-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.

Original languageEnglish (US)
Pages (from-to)11327-11333
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996

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