title: Upregulation of major histocompatibility complex class I on liver cells by hepatitis C virus core protein via p53 and TAP1 impairs natural killer cell cytotoxicity.
abstract: The mechanisms of immune evasion and the role of the early immune response in chronic infection caused by hepatitis C virus (HCV) are still unclear. Here, we present evidence for a cascade of molecular events that the virus initiates to subvert the innate immune attack. The HCV core protein induced p53-dependent gene expression of TAP1 (transporter associated with antigen processing 1) and consecutive major histocompatibility complex (MHC) class I upregulation. Moreover, in p53-deficient liver cell lines, only reconstitution with wild-type p53, but not mutated p53 lacking DNA binding capacity, showed this effect. As a consequence of increased MHC class I expression, a significantly downregulated cytotoxic activity of natural killer (NK) cells against HCV core-transfected liver cells was observed, whereas lysis by HCV-specific cytotoxic T cells was not affected. These results demonstrate a way in which HCV avoids recognition by NK cells that may contribute to the establishment of a chronic infection.
authors.affiliation: Division of Immunogenetics, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.forename: Jens
authors.initials: J
authors.lastname: Encke
authors.forename: Sören T
authors.initials: ST
authors.lastname: Eichhorst
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000503:physiopathology / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; D016159:Tumor Suppressor Protein p53; D014758:Viral Core Proteins