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Journal of Virology, August 2002, p. 8189-8199, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8189-8199.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Alpha Interferon Inhibits Hepatitis C Virus Replication in Primary Human Hepatocytes Infected In Vitro

Valérie Castet,1 Chantal Fournier,1,2 Alexandre Soulier,3 Rozenn Brillet,3 Joliette Coste,2 Dominique Larrey,1,4 Daniel Dhumeaux,3,5 Patrick Maurel,1 and Jean-Michel Pawlotsky3*

INSERM U128,1 Etablissement Français du Sang "Pyrénées-Méditerranée,",2 Digestive Disease Institute, Saint-Eloi Hospital, University of Montpellier, Montpellier,4 Department of Virology (EA 3489),3 Department of Hepatology and Gastroenterology, Henri Mondor Hospital, University of Paris XII, Créteil, France5

Received 6 November 2001/ Accepted 23 May 2002

Chronic hepatitis C is a common cause of liver disease, the complications of which include cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis C is based on the use of alpha interferon (IFN-{alpha}). Recently, indirect evidence based on mathematical modeling of hepatitis C virus (HCV) dynamics during human IFN-{alpha} therapy suggested that the major initial effect of IFN-{alpha} is to block HCV virion production or release. Here, we used primary cultures of healthy, uninfected human hepatocytes to show that: (i) healthy human hepatocytes can be infected in vitro and support HCV genome replication, (ii) hepatocyte treatment with IFN-{alpha} results in expression of IFN-{alpha}-induced genes, and (iii) IFN-{alpha} inhibits HCV replication in infected human hepatocytes. These results show that IFN-{alpha} acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-{alpha}.

* Corresponding author. Mailing address: Service de Virologie, Hôpital Henri Mondor, 51 ave. du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Phone: (33) 1 4981 2827. Fax: (33) 1 4981 2839. E-mail: jean-michel.pawlotsky{at}hmn.ap-hop-paris.fr.

Journal of Virology, August 2002, p. 8189-8199, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8189-8199.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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