Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs

Michael Frese, Verena Schwärzle, Kerstin Barth, Nicole Krieger, Volker Lohmann, Sabine Mihm, Otto Haller, Ralf Bartenschlager

Research output: Contribution to journalArticle

264 Citations (Scopus)

Abstract

Persistent infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. All treatments known so far rely on the antiviral activity of interferon alfa (IFN-α) that is given alone or in combination with ribavirin. Unfortunately, only a fraction of the patients dear the virus during therapy and for those who do not respond there is currently no alternative treatment. Selectable subgenomic HCV RNAs (replicons) have been recently used to investigate the effect of IFN-α on HCV replication. However, it has not yet been analyzed whether other cytokines also play a role in the innate immune response against HCV. Here we show that IFN-γ inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons. We further show that the inhibitory action of IFN-γ does not rely on the production of nitric oxide or the depletion of tryptophan. In conclusion, our results suggest that cytotoxic T cells and natural killer cells may contribute to HCV clearance not only by cell killing but also by producing IFN-γ, thereby enhancing the intracellular inhibition of viral replication.

Original languageEnglish
Pages (from-to)694-703
Number of pages10
JournalHepatology
Volume35
Issue number3
DOIs
Publication statusPublished - 1 Jan 2002

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Hepacivirus
Interferons
Interferon-alpha
RNA
Replicon
Ribavirin
Chronic Hepatitis
Virus Replication
Innate Immunity
Tryptophan
Natural Killer Cells
Liver Cirrhosis
Antiviral Agents
Hepatocellular Carcinoma
Nitric Oxide
Therapeutics
Cytokines
Viruses
T-Lymphocytes
Infection

Cite this

Frese, M., Schwärzle, V., Barth, K., Krieger, N., Lohmann, V., Mihm, S., ... Bartenschlager, R. (2002). Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology, 35(3), 694-703. https://doi.org/10.1053/jhep.2002.31770
Frese, Michael ; Schwärzle, Verena ; Barth, Kerstin ; Krieger, Nicole ; Lohmann, Volker ; Mihm, Sabine ; Haller, Otto ; Bartenschlager, Ralf. / Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs. In: Hepatology. 2002 ; Vol. 35, No. 3. pp. 694-703.
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Frese, M, Schwärzle, V, Barth, K, Krieger, N, Lohmann, V, Mihm, S, Haller, O & Bartenschlager, R 2002, 'Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs', Hepatology, vol. 35, no. 3, pp. 694-703. https://doi.org/10.1053/jhep.2002.31770

Interferon-γ inhibits replication of subgenomic and genomic hepatitis C virus RNAs. / Frese, Michael; Schwärzle, Verena; Barth, Kerstin; Krieger, Nicole; Lohmann, Volker; Mihm, Sabine; Haller, Otto; Bartenschlager, Ralf.

In: Hepatology, Vol. 35, No. 3, 01.01.2002, p. 694-703.

Research output: Contribution to journalArticle

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