Cowpox virus exploits the endoplasmic reticulum retention pathway to inhibit MHC class I transport to the cell surface |
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Authors: | Byun Minji Wang Xiaoli Pak Melissa Hansen Ted H Yokoyama Wayne M |
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Institution: | Howard Hughes Medical Institute, Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. |
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Abstract: | 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. |
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