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First posted online 18 January 2001 ARTICLE ABSTRACT
Rec 23 November 2000; Acc 11 January 2001 DOI: 10.1099/vir.0.17563-0

Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway

Michael Frese,1 Thomas Pietschmann,2 Darius Moradpour,3 Otto Haller1 and Ralf Bartenschlager2

1 Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany
2 Institut für Virologie, Universität Mainz, Obere Zahlbacher Str. 67, D-55131 Mainz, Germany
3 Abteilung Innere Medizin II, Medizinische Universitätsklinik Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany

Hepatitis C virus (HCV) persists in the majority of infected individuals and is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is currently treated with interferon (IFN)-alpha or with a combination of IFN-alpha and ribavirin. The availability of an HCV replicon system (Lohmann et al., Science 285, 110–113, 1999) allowed the investigation of the effects of IFN on genuine HCV replication in cultured cells. It is shown here that IFN-alpha inhibits subgenomic HCV RNA replication in HuH-7 human hepatoma cells. Immunofluorescence, Western blot and Northern blot analysis revealed that levels of both HCV protein and replicon RNA were reduced after treatment with IFN-alpha in a dose-dependent manner. In further experiments, it was investigated whether MxA plays a role in the inhibition of HCV. The human MxA protein is an IFN-induced GTPase that has antiviral activity against various RNA viruses. However, HCV RNA replication was not affected in transfected HuH-7 cells that transiently overexpressed MxA. Moreover, a dominant-negative mutant of MxA did not interfere with the antiviral activity of IFN-alpha against HCV RNA replication. Taken together, these results demonstrate that IFN-alpha inhibits HCV replicons via an MxA-independent pathway.

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© 2001 SGM

This article is now available in the April 2001 print issue of JGV (vol. 82, 723–733). The complete issue of the journal may be seen in electronic form on JGV Online.