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Journal of Virology, December 2002, p. 12974-12980, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12974-12980.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Hepatocyte Nuclear Factor 3ß Inhibits Hepatitis B Virus Replication In Vivo{dagger}

Krista E. Banks,1 Aimee L. Anderson,1 Hong Tang,1,2 Douglas E. Hughes,3 Robert H. Costa,3 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 China,2 Department of Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois 606073

Received 13 August 2002/ Accepted 16 September 2002

Hepatitis B virus (HBV) transgenic mice expressing rat hepatocyte nuclear factor 3ß (HNF3ß) were generated by breeding HBV transgenic mice with transgenic mice that constitutively overexpress the rat HNF3ß polypeptide in the liver. HBV 3.5-, 2.4- and 2.1-kb transcripts were reduced 2- to 4-fold in these mice relative to the HBV transgenic mouse controls. In contrast, the abundance of viral replication intermediates was profoundly reduced in HBV transgenic mice by overexpression of HNF3ß. This results, in part, from the preferential reduction in the level of the pregenomic 3.5-kb RNA relative to the precore 3.5-kb RNA. Therefore, it is apparent that increased expression of HNF3ß modestly reduces viral transcription and dramatically inhibits replication in vivo in the HBV transgenic mouse. This suggests that altering the activity of this transcription factor in vivo in chronic HBV carriers might be therapeutically beneficial.


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

{dagger} Publication no. 14998-CB from The Scripps Research Institute.


Journal of Virology, December 2002, p. 12974-12980, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12974-12980.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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