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Originally published In Press as doi:10.1074/jbc.C100729200 on January 7, 2002

J. Biol. Chem., Vol. 277, Issue 10, 7645-7647, March 8, 2002
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ACCELERATED PUBLICATION
Antiviral Activity of Interferon-alpha against Hepatitis B Virus Can Be Studied in Non-hepatic Cells and Is Independent of MxA*

Andreas RangDagger , Michael Bruns, Tilman Heise, and Hans Will

From the Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistraße 52, 20251 Hamburg, Germany

It is well established that interferon-alpha can induce non-cytotoxic intracellular suppression of hepatitis B virus replication, but the mechanisms involved are unclear. Cell culture studies to characterize these mechanisms are restricted, in part because hepatitis B virus replicates almost exclusively in liver-derived cells. To overcome this limitation we used a cytomegalovirus promoter-controlled hepatitis B virus expression system, which leads to intracellular viral replication even in non-hepatic cell lines. In this experimental system interferon-alpha treatment specifically suppressed viral replication demonstrating that antiviral activities against hepatitis B virus are not restricted to hepatic cells. Furthermore, the interferon-inducible MxA protein was recently reported to play a key role in the antiviral action of interferon-alpha against hepatitis B virus. Our data demonstrate that interferon-alpha also suppresses hepatitis B virus replication in MxA-deficient HEp2 cells, indicating that MxA is not essential for these activities. Taken together, our data imply that the experimental approach presented can also be adapted to established cell lines which are deficient in parts of the signal transduction pathway or other elements located further downstream, providing important insights into mechanisms specifically suppressing hepatitis B virus.


* This work was supported by grants from the Bundesministerium für Bildung und Forschung and the Deutsche Forschungsgemeinschaft. The Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie is supported by the Bundesministerium für Gesundheit und the Freie and Hansestadt Hamburg.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Bundesinstitut für Gesundheitlichen Verbraucherschutz und Veterinärmedizin, Thielallee 88-92, 14195 Berlin, Germany. Tel.: 49-188-8412-3716; Fax: 49-188-8412-3635; E-mail: a.rang@bgvv.de.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


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