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Journal of Virology, September 2001, p. 8516-8523, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8516-8523.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Effect of Alpha Interferon on the Hepatitis C Virus Replicon

Ju-Tao Guo,1 Vadim V. Bichko,2 and Christoph Seeger1,*

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111,1 and Anadys Pharmaceuticals, San Diego, California 921212

Received 13 March 2001/Accepted 12 June 2001

Chronic hepatitis C virus (HCV) infections can be cured only in a fraction of patients treated with alpha interferon (IFN-alpha ) and ribavirin combination therapy. The mechanism of the IFN-alpha response against HCV is not understood, but evidence for a role for viral nonstructural protein 5A (NS5A) in IFN resistance has been provided. To elucidate the mechanism by which NS5A and possibly other viral proteins inhibit the cellular antiviral program, we have constructed a subgenomic replicon from a known infectious HCV clone and demonstrated that it has an approximately 1,000-fold-higher transduction efficiency than previously used subgenomes. We found that IFN-alpha reduced replication of HCV subgenomic replicons approximately 10-fold. The estimated half-life of viral RNA in the presence of the cytokine was about 12 h. HCV replication was sensitive to IFN-alpha independently of whether the replicon expressed an NS5A protein associated with sensitivity or resistance to the cytokine. Furthermore, our results indicated that HCV replicons can persist in Huh7 cells in the presence of high concentrations of IFN-alpha . Finally, under our conditions, selection for IFN-alpha -resistant variants did not occur.

* Corresponding author. Mailing address: Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: (215) 718-4312. Fax: (215) 728-4329. E-mail: c_seeger{at}fccc.edu.

Journal of Virology, September 2001, p. 8516-8523, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8516-8523.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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