Cowpox Virus Exploits the Endoplasmic Reticulum Retention Pathway to Inhibit MHC Class I Transport to the Cell Surface

Minji Byun, Xiaoli Wang, Melissa Pak, Ted H. Hansen, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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.

Original languageEnglish
Pages (from-to)306-315
Number of pages10
JournalCell Host and Microbe
Volume2
Issue number5
DOIs
StatePublished - Nov 15 2007

Keywords

  • CELLBIO
  • MICROBIO
  • MOLIMMUNO

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