6533b825fe1ef96bd128280c
RESEARCH PRODUCT
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
Barbara SeligerPeter H. KrammerJens EnckeChristine S. FalkK HerzerAxel UlsenheimerSören T. Eichhorstsubject
Cytotoxicity ImmunologicImmunologyAntigen presentationHepacivirusMajor histocompatibility complexMicrobiologyCell LineNatural killer cellAntigenVirologyMHC class ImedicineHumansATP Binding Cassette Transporter Subfamily B Member 2Cells CulturedLymphokine-activated killer cellbiologyViral Core ProteinsHistocompatibility Antigens Class IHepatitis C ChronicNatural killer T cellVirologyUp-RegulationKiller Cells Naturalmedicine.anatomical_structureInsect ScienceImmunologyHepatocytesbiology.proteinPathogenesis and ImmunityATP-Binding Cassette TransportersTumor Suppressor Protein p53CD8description
ABSTRACTThe 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-08-01 | Journal of Virology |