Identification of a specific gene expression pattern associated with HCV-induced pathogenesis in HCV- and HCV/HIV-infected individuals

Kathie Anne Walters, Maria W. Smith, Sampa Pal, Jill C. Thompson, Matthew J. Thomas, Matthew M. Yeh, David L. Thomas, Matthew Fitzgibbon, Sean Proll, Nelson Fausto, David R. Gretch, Robert L. Carithers, Margaret C. Shuhart, Michael G. Katze

Research output: Contribution to journalArticlepeer-review

Abstract

Gene expression profiling was performed on liver biopsies from 28 patients (12 HCV and 16 HCV/HIV infected) in an attempt to understand the mechanisms of HCV liver disease in the presence and absence of HIV coinfection. The data were compared with clinical observations and a gene expression database obtained for transplant HCV-infected samples. This is the first report of functional genomics being used to compare intrahepatic gene expression profiles of HCV- and HCV/HIV-infected individuals. Significantly, the intrahepatic global gene expression profiles do not differ between HCV- and HCV/HIV-infected individuals. However, a subset of patients was identified who share a specific pattern of gene expression, termed the enhanced gene expression (EGE) pattern. Specifically, the EGE (+) patients show a dramatic decreased expression of multiple genes associated with the FAS-apoptosis pathway and increased expression of lymphocyte adhesion molecules and lymphocyte-specific genes. The EGE (+) patients also have partially impaired Type I and II IFN-mediated antiviral responses, including a lack of induction of the anti-fibrogenic cytokine IFN-γ. Importantly, the pattern of gene expression observed in EGE (+) patients has similarities to patients who developed fibrosis within 1 year of receiving a liver transplant.

Original languageEnglish (US)
Pages (from-to)453-464
Number of pages12
JournalVirology
Volume350
Issue number2
DOIs
StatePublished - Jul 5 2006

Keywords

  • Apoptosis
  • Fibrosis
  • Interferon
  • Microarray
  • Viral hepatitis

ASJC Scopus subject areas

  • Virology

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