Interferon type I gene expression in chronic hepatitis C

Sabine Mihm, Michael Frese, Volker Meier, Perdita Wietzke-Braun, Jens Gerd Scharf, Ralf Bartenschlager, Giuliano Ramadori

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79 Citations (Scopus)

Abstract

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-α, IFN-β, and IFN-λ 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.

Original languageEnglish
Pages (from-to)1148-1159
Number of pages12
JournalLaboratory Investigation
Volume84
Issue number9
DOIs
Publication statusPublished - 1 Sep 2004
Externally publishedYes

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    Mihm, S., Frese, M., Meier, V., Wietzke-Braun, P., Scharf, J. G., Bartenschlager, R., & Ramadori, G. (2004). Interferon type I gene expression in chronic hepatitis C. Laboratory Investigation, 84(9), 1148-1159. https://doi.org/10.1038/labinvest.3700135