Steatosis and intrahepatic lymphocyte recruitment in hepatitis C virus transgenic mice

Tonino Alonzi, Chiara Agrati, Barbara Costabile, Carla Cicchini, Laura Amicone, Claudio Cavallari, Carlo Della Rocca, Antonella Folgori, Cristina Fipaldini, Fabrizio Poccia, Nicola La Monica, Marco Tripodi

Research output: Contribution to journalArticlepeer-review

Abstract

To assess the effects of constitutive hepatitis C virus (HCV) gene expression on liver, transgenic mice carrying the entire HCV open reading frame inserted in the α1 antitrypsin (A1AT) gene were generated. Expression of A1AT/HCV mRNA was found to be mainly limited to perivascular areas of the liver as indicated by in situ hybridization analysis. HCV core protein was detected in Western blots of liver extracts, whereas the expression of E2, NS3 and NS5 proteins was revealed by immunostaining of liver samples using HCV-specific antisera. Histological analysis of HCV transgenic mice showed that these animals develop extensive steatosis, but very little necrosis of liver tissue. Moreover, a consistent T cell infiltrate and a slight hepatocyte proliferation were observed. Phenotypic analysis of cells infiltrating the liver indicated that recruitment and/or expansion of residing CD8+, NK, NKT and γδ T cells occurred in transgenic animals. Among these cells, a large fraction of CD8+ T lymphocytes released mainly IL-10 and, to a lesser extent, IFN-γ upon mitogenic stimulation in vitro. Furthermore, both intrahepatic lymphocytes and splenocytes did not produce cytokines in response to HCV antigens. Thus, these data indicate that constitutive expression of HCV proteins may be responsible for intrahepatic lymphocyte recruitment in absence of viral antigen recognition. This response is likely to be driven by virus-induced cellular factors and may play a significant role in the immunopathology of chronic HCV infection and liver disease.

Original languageEnglish
Pages (from-to)1509-1520
Number of pages12
JournalJournal of General Virology
Volume85
Issue number6
DOIs
Publication statusPublished - Jun 2004

ASJC Scopus subject areas

  • Virology
  • Immunology

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