Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains
Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains
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DOI：
10.1073/pnas.93.21.11327
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发表时间：
1996-10-15
影响因子：
11.1
通讯作者：
Ploegh, HL
中科院分区：
文献类型：
--
作者：
Jones, TR;Wiertz, EJHJ;Ploegh, HL
US 11和US 2开放阅读框的人巨细胞病毒（HCMV）早期糖蛋白产物导致主要组织相容性复合体（MHC）I类重链的周转增加。由于US 2与另一个HCMV基因（US 3）同源，我们假设US 3基因产物也可能影响MHC I类分子的表达。在组成型表达HCMV US 3基因的细胞中，NHC I类重链与β 2-微球蛋白形成稳定的复合物。然而，在US 3+细胞中，MHC I类重链的N-连接聚糖的成熟受损。US 3的糖蛋白产物（gpUS 3）主要以高甘露糖形式存在，并与β 2-微球蛋白相关的I类重链共免疫沉淀。与对照细胞一样，在US 3+细胞的表面上检测到稳态的成熟I类分子。在US 3+细胞中观察到重链的大量核周蓄积。这些数据表明，gpUS 3损害了MHC I类重链从内质网的流出。
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, NHC 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.