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 journalArticlepeer-review

327 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

ASJC Scopus subject areas

  • General

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