Byun Minji, Wang Xiaoli, Pak Melissa, Hansen Ted H, Yokoyama Wayne M
Howard Hughes Medical Institute, Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell Host Microbe. 2007 Nov 15;2(5):306-15. doi: 10.1016/j.chom.2007.09.002.
Major histocompatibility complex (MHC) class I molecules assemble with peptides in the ER lumen and are transported via Golgi to the plasma membrane for recognition by T cells. Inhibiting MHC assembly, transport, and surface expression are common viral strategies of evading immune recognition. Cowpox virus, a clinically relevant orthopoxvirus, downregulates MHC class I expression on infected cells. However, the viral protein(s) and mechanisms responsible are unknown. We identify CPXV203 as a cowpox virus protein that associates with fully assembled MHC class I molecules and blocks their transport through the Golgi. A C-terminal KTEL motif in CPXV203 closely resembles the canonical ER retention motif KDEL and is required for CPXV203 function, indicating that a physiologic pathway is exploited to retain MHC class I in the ER. This viral mechanism for MHC class I downregulation may explain virulence differences between clinical isolates of orthopoxviruses.
主要组织相容性复合体（MHC）I类分子在内质网腔中与肽组装，并通过高尔基体运输到质膜以供T细胞识别。抑制MHC组装、运输和表面表达是病毒逃避免疫识别的常见策略。牛痘病毒是一种具有临床相关性的正痘病毒，可下调感染细胞上的MHC I类表达。然而，负责的病毒蛋白和机制尚不清楚。我们鉴定出CPXV203是一种牛痘病毒蛋白，它与完全组装好的MHC I类分子结合，并阻止它们通过高尔基体运输。CPXV203中的C末端KTEL基序与典型的内质网滞留基序KDEL非常相似，是CPXV203功能所必需的，这表明利用了一种生理途径将MHC I类保留在内质网中。这种MHC I类下调的病毒机制可能解释了正痘病毒临床分离株之间的毒力差异。
