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Journal of Virology, September 2002, p. 8572-8581, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8572-8581.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mechanisms of Inhibition of Nuclear Hormone Receptor-Dependent Hepatitis B Virus Replication by Hepatocyte Nuclear Factor 3ß{dagger}

Hong Tang1,2 and Alan McLachlan1*

Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037,1 Viral Hepatitis Research Unit, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China2

Received 8 February 2002/ Accepted 6 June 2002

The nuclear hormone receptors hepatocyte nuclear factor 4 (HNF4) and the retinoid X {alpha} (RXR{alpha}) plus the peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) heterodimer support hepatitis B virus (HBV) replication in nonhepatoma cells. Hepatocyte nuclear factor 3 (HNF3) inhibits nuclear hormone receptor-mediated viral replication. Inhibition of HBV replication by HNF3ß is associated with the preferential reduction in the level of the pregenomic RNA compared with that of precore RNA. Hepatitis B e antigen (HBeAg), encoded by the precore RNA, mediates part of the inhibition of viral replication by HNF3ß. The amino-terminal transcriptional activation domain of HNF3ß is essential for the inhibition of HBV replication. The activation of transcription by HNF3 from HBV promoters downstream from the nucleocapsid promoter appears to contribute indirectly to the reduction in the steady-state level of 3.5-kb HBV RNA, possibly by interfering with the elongation rate of these transcripts. Therefore, transcriptional interference mediated by HNF3 may also regulate HBV RNA synthesis and viral replication.

* Corresponding author. Mailing address: Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8097. Fax: (858) 784-2513. E-mail: mclach{at}scripps.edu.

{dagger} Publication number 14563-CB from The Scripps Research Institute, La Jolla, Calif.

Journal of Virology, September 2002, p. 8572-8581, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8572-8581.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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