Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes.
Viruses which cause persistence in the naturally infected host are predicted to have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes significant morbidity and mortality in immunocompromised patients yet persists without clinical manifestations in seropositive individuals who have normal immune function. We report that HCMV infection in vitro impairs major histocompatibility complex class I (MHC-I) assembly accompanied by resistance to killing by cytotoxic CD8+ T lymphocytes. Pulse-chase metabolic labelling experiments show that MHC-I complexes continue to be assembled by both uninfected and HCMV-infected cells. However, MHC-I molecules are unstable in HCMV-infected cells and are rapidly broken down. Endoglycosidase H treatment of immunoprecipitates indicates that the breakdown of MHC-I complexes in HCMV-infected cells occurs primarily in a pre-Golgi compartment. Interference with normal MHC-I assembly and expression, if relevant in vivo, may have implications for the restriction of the diversity of the CD8+ cytotoxic T lymphocyte repertoire directed against HCMV antigens and may be an important mechanism of viral persistence.
Warren
A P
AP
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom.
Ducroq
D H
DH
Lehner
P J
PJ
Borysiewicz
L K
LK
D016827:CD8 Antigens / Q000276:immunology; D016923:Cell Death; D002460:Cell Line; D002860:Chromium Radioisotopes; D003587:Cytomegalovirus / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005434:Flow Cytometry; D006596:Hexosaminidases / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016827:CD8 Antigens; D002860:Chromium Radioisotopes; D015395:Histocompatibility Antigens Class I; D006596:Hexosaminidases