the epstein-barr virus g-protein-coupled receptor contributes to immune evasion by targeting mhc class i molecules for degradation巴尔病毒g-protein-coupled受体导致免疫逃避我针对类mhc分子降解.pdf

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation 1 1 2 1 1 Jianmin Zuo , Andrew Currin , Bryan D. Griffin , Claire Shannon-Lowe , Wendy A. Thomas , Maaike E. 2 3 1 Ressing , Emmanuel J. H. J. Wiertz , Martin Rowe * 1 Cancer Research-UK Institute for Cancer Studies, School of Cancer Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, 2 Center of Infectious Diseases and Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands, 3 Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, The Netherlands Abstract Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I simil