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Journal of Virology, December 1999, p. 10377-10386, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferatorsdagger

Luca G. Guidotti,1 Carrie M. Eggers,2 Anneke K. Raney,2 Susan Y. Chi,2 Jeffrey M. Peters,3 Frank J. Gonzalez,3 and Alan McLachlan2,*

Department of Molecular and Experimental Medicine1 and Department of Cell Biology,2 The Scripps Research Institute, La Jolla, California 92037, and Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 208923

Received 11 June 1999/Accepted 30 August 1999

The role of the peroxisome proliferator-activated receptor alpha  (PPARalpha ) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARalpha . HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPARalpha but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice.

* 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 no. 12404-CB from The Scripps Research Institute.

Journal of Virology, December 1999, p. 10377-10386, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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