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

Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11327-33. doi: 10.1073/pnas.93.21.11327.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Cell Line
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology
  • Cytomegalovirus / physiology*
  • DNA, Viral
  • Endoplasmic Reticulum / immunology
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation, Viral / immunology
  • Glutathione Transferase
  • Glycoproteins
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / biosynthesis*
  • Humans
  • Immediate-Early Proteins / analysis
  • Immediate-Early Proteins / metabolism*
  • Membrane Proteins
  • Molecular Sequence Data
  • Open Reading Frames
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators / metabolism*
  • Transfection
  • beta 2-Microglobulin / isolation & purification
  • beta 2-Microglobulin / metabolism

Substances

  • Antibodies, Monoclonal
  • DNA, Viral
  • Glycoproteins
  • Histocompatibility Antigens Class I
  • Immediate-Early Proteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • US3 protein, cytomegalovirus
  • beta 2-Microglobulin
  • Glutathione Transferase

Associated data

  • GENBANK/X17403