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Journal of Virology, January 1999, p. 474-481, Vol. 73, No. 1
Department of Molecular and Experimental
Medicine, The Scripps Research Institute, La Jolla, California
92037,1 and
Institut für Biochemie
und Molekulare Zellbiologie, Georg-August-Universität
Göttingen, D-37073 Göttingen,
Germany2
Received 20 July 1998/Accepted 7 October 1998
Hepatitis B virus (HBV) gene expression is downregulated in the
liver of HBV transgenic mice by a posttranscriptional
mechanism that is triggered by the local production of gamma interferon (IFN-
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Hepatitis B Virus RNA-Binding Proteins Associated with
Cytokine-Induced Clearance of Viral RNA from the Liver of
Transgenic Mice
) and tumor necrosis factor alpha (TNF-
) during intrahepatic inflammation (hepatitis). The molecular basis for this
antiviral effect is unknown. In this study, we identified three HBV
RNA-binding liver nuclear proteins (p45, p39, and p26) the relative
abundance of which correlates with the abundance of HBV RNA in response to the induction of IFN-
and TNF-
. All three proteins bind
to a 91-bp element located at the 5' end of a previously defined posttranscriptional regulatory element that is thought to mediate the
nuclear export of HBV RNA. The presence of p45 correlates directly with
the presence of HBV RNA, being detectable under baseline conditions
when the viral RNA is abundant and undetectable when the viral RNA
disappears in response to IFN-
and TNF-
. In contrast, p26 is
inversely related to HBV RNA, being detectable only when the viral RNA
disappears following cytokine activation. Finally, p39 is
constitutively expressed, and its abundance and mobility appear to be
slightly increased by cytokine activation. These results suggest a
model in which hepatocellular HBV RNA content might be controlled by
the stabilizing and/or destabilizing influences of these RNA-binding
proteins whose activity is regulated by cytokine-induced signaling pathways.
*
Corresponding author. Mailing address: Department of
Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-8228. Fax: (619) 784-2160. E-mail: fchisari{at}scripps.edu.
Manuscript no. 11630-MEM from The Scripps Research Institute.
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