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 Nelson, Hidde L. Ploegh

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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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Major Histocompatibility Complex
Cytomegalovirus
Glycoproteins
Genes
Mannose
Endoplasmic Reticulum
Open Reading Frames
Polysaccharides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. / Jones, Thomas R.; Wiertz, Emmanuel J H J; Sun, Lei; Fish, Kenneth N.; Nelson, Jay; Ploegh, Hidde L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 21, 15.10.1996, p. 11327-11333.

Research output: Contribution to journalArticle

Jones, Thomas R. ; Wiertz, Emmanuel J H J ; Sun, Lei ; Fish, Kenneth N. ; Nelson, Jay ; Ploegh, Hidde L. / Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 21. pp. 11327-11333.
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