Interferon type I gene expression in chronic hepatitis C

Lab Invest. 2004 Sep;84(9):1148-59. doi: 10.1038/labinvest.3700135.


Hepatitis C virus (HCV) frequently causes chronic liver disease. The cause of viral persistence might be an inappropriate type I interferon (IFN) induction. To analyze the host's IFN response in chronic hepatitis C, we measured the transcription level of type I IFN genes as well as type I IFN-regulated genes in liver tissue and corresponding blood samples from patients with chronic hepatitis C, nonviral liver diseases, and a suspected but later excluded liver disease. Competitive and real-time RT-PCR assays were used to quantify the messenger RNA (mRNA) levels of all known IFN-alpha, IFN-beta, and IFN-lambda genes and those of some IFN-regulated genes. We failed to detect any hepatic type I IFN mRNA induction, although liver tissue of chronic hepatitis C patients contained high numbers of some type I IFN-inducible effector mRNA molecules. Analysis of peripheral blood samples, however, showed a clear type I IFN induction. Parallel experiments employing HCV replicon cell lines revealed that replication of HCV RNA is not sufficient to induce any type I IFN nor to induce directly type I IFN-regulated genes such as MxA. In conclusion, our data provide evidence for the absence of an induction of type I IFN genes by HCV in the human liver and argue for a further development of type I IFN-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Viral*
  • Hepacivirus / genetics*
  • Hepacivirus / growth & development
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / pathology
  • Hepatocytes / virology
  • Humans
  • Interferon Type I / genetics*
  • Interferon Type I / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • RNA, Viral / analysis
  • Replicon / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Virus Replication / physiology


  • Interferon Type I
  • RNA, Messenger
  • RNA, Viral