HCV inhibits antigen processing and presentation and induces oxidative stress response in gastric mucosa

Valli De Re, Maria Paola Simula, Renato Cannizzaro, Domenico Sansonno, Vincenzo Canzonieri, Annunziata Gloghini, Antonino Carbone, Alfonso Colombatti, Maria Dolores Marin, Mariangela De Zorzi, Giuseppe Toffoli

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1290-1299
Number of pages10
JournalProteomics - Clinical Applications
Volume2
Issue number9
DOIs
Publication statusPublished - Sep 2008

Keywords

  • Cancer
  • Hepatitis C virus
  • Inflammation
  • Proteomic
  • Ubiquinol-cytochrome-C-reductase

ASJC Scopus subject areas

  • Clinical Biochemistry

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