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HCV inhibits antigen processing and presentation and induces oxidative stress response in gastric mucosa
Author(s) -
De Re Valli,
Simula Maria Paola,
Cannizzaro Renato,
Sansonno Domenico,
Canzonieri Vincenzo,
Gloghini Annunziata,
Carbone Antonino,
Colombatti Alfonso,
Marin Maria Dolores,
De Zorzi Mariangela,
Toffoli Giuseppe
Publication year - 2008
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200800059
Subject(s) - hepatitis c virus , biology , antigen , oxidative stress , antigen presentation , immunology , antigen processing , immune system , hepatitis c , virus , t cell , biochemistry
Productive hepatitis C virus (HCV) infection appears to be primarily confined to the liver. However, a wide variety of extrahepatic disease manifestations are associated with the infection and HCV RNA has been frequently detected in gastric mucosa. The present study aims to determine molecular alterations present in vivo in the stomach where HCV expression does not induce a carcinoma but a lymphoma, thus extending the knowledge of alterations in intracellular pathways consequent to HCV infection. We compared, by 2‐D DIGE, the gastric protein expression profile from six HCV positive and six HCV negative samples lacking neoplastic or dysplastic conditions. In HCV positive tissue we observed a down regulation of proteins involved in MHC maturation and assembly, antigen processing and presentation and ER stress, in addition to an up regulation of proteins involved in cellular oxidative stress responses. Ubiquinol‐cytochrome‐C‐reductase (UQCRFS1), part of the mitochondrial respiratory chain complex‐III, was identified as the most up regulated protein. Data were confirmed by Western blot and immunohistochemistry. Our results demonstrate a HCV negative influence on the different pathways that determine antigen processing and presentation via MHC‐I and the cellular attempts to counteract HCV induced oxidative stress. Both these processes facilitate immune escape and cell survival and probably contribute to HCV chronicization.