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
| Autor: | Barbara Seliger, Peter H. Krammer, Jens Encke, Christine S. Falk, K Herzer, Axel Ulsenheimer, Sören T. Eichhorst |
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| Rok vydání: | 2003 |
| Předmět: |
Cytotoxicity
Immunologic Immunology Antigen presentation Hepacivirus Major histocompatibility complex Microbiology Cell Line Natural killer cell Antigen Virology MHC class I medicine Humans ATP Binding Cassette Transporter Subfamily B Member 2 Cells Cultured Lymphokine-activated killer cell biology Viral Core Proteins Histocompatibility Antigens Class I Hepatitis C Chronic Natural killer T cell Up-Regulation Killer Cells Natural medicine.anatomical_structure Insect Science Hepatocytes biology.protein Pathogenesis and Immunity ATP-Binding Cassette Transporters Tumor Suppressor Protein p53 CD8 |
| Zdroj: | Journal of Virology. 77:8299-8309 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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