HUMAN CYTOMEGALOVIRUS US3 IMPAIRS TRANSPORT AND MATURATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HEAVY-CHAINS

The human cytomegalovirus (HCMV) early glycoprotein products of the US 11 and US2 open reading frames cause increased turnover of major histo compatibility complex (MHC) class I heavy chains. Since US2 is homolog ous to another HCMV gene (US3), we hypothesized that the US3 gene prod uct also may affect MHC class I expression. In cells constitutively ex pressing the HCMV US3 gene, NHC class I heavy chains formed a stable c omplex with beta(2)-microglobulin. However, maturation of the N-linked glycan of MHC class I heavy chains was impaired in US3+ cells. The gl ycoprotein 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 perinu clear accumulation of heavy chains was observed in US3+ cells. The dat a suggest that gpUS3 impairs egress of MHC class I heavy chains from t he endoplasmic reticulum.