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Journal of Virology, January 2003, p. 1227-1236, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1227-1236.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Searching for Interferon-Induced Genes That Inhibit Hepatitis B Virus Replication in Transgenic Mouse Hepatocytes{dagger}

Stefan F. Wieland,1* Raquel G. Vega,2 Rolf Müller,3 Claire F. Evans,3 Brian Hilbush,3 Luca G. Guidotti,1 J. Gregor Sutcliffe,4 Peter G. Schultz,2 and Francis V. Chisari1

Department of Molecular and Experimental Medicine,1 Department of Molecular Biology, The Scripps Research Institute,4 Digital Gene Technologies, Inc., La Jolla, California 92037,3 Genomics Institute of the Novartis Research Foundation, San Diego, California 921212

Received 9 September 2002/ Accepted 24 October 2002

We have previously shown that alpha/beta interferon (IFN-{alpha}/ß) and IFN-{gamma} inhibit hepatitis B virus (HBV) replication noncytopathically in the livers of HBV transgenic mice and in hepatocyte cell lines derived from these mice. The present study was designed to identify transcriptionally controlled hepatocellular genes that are tightly associated with the inhibition of HBV replication and that might, therefore, mediate the antiviral effect of these cytokines. Twenty-nine genes were identified, many of which have known or potential antiviral activity. Notably, multiple components of the immunoproteasome and ubiquitin-like proteins were strongly induced by both IFN-{alpha}/ß and IFN-{gamma}, as were a number of GTP-binding proteins, including GTPases with known antiviral activity, chemokines, signaling molecules, and miscellaneous genes associated with antigen processing, DNA-binding, or cochaperone activity and several expressed sequence tags. The results suggest that one or more members of this relatively small subset of genes may mediate the antiviral effect of IFN-{alpha} and IFN-{gamma} against HBV. We have already exploited this information by demonstrating that the antiviral activity of IFN-{alpha} and IFN-{gamma} is proteasome dependent.


* Corresponding author. Mailing address: Department of Molecular and Experimental Medicine, SBR-10, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-2406. Fax: (858) 784-2960. E-mail: swieland{at}scripps.edu.

{dagger} This is paper no. 14895-MEM from the Scripps Research Institute.


Journal of Virology, January 2003, p. 1227-1236, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.1227-1236.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Wieland, S., Thimme, R., Purcell, R. H., Chisari, F. V. (2004). Genomic analysis of the host response to hepatitis B virus infection. Proc. Natl. Acad. Sci. USA 101: 6669-6674 [Abstract] [Full Text]  
  • Robek, M. D., Boyd, B. S., Wieland, S. F., Chisari, F. V. (2004). Signal transduction pathways that inhibit hepatitis B virus replication. Proc. Natl. Acad. Sci. USA 101: 1743-1747 [Abstract] [Full Text]