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Journal of Virology, December 1999, p. 10377-10386, Vol. 73, No. 12
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
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 Proliferators
(PPAR
) 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 PPAR
. HBV transgenic mice lacking
this nuclear hormone receptor showed similar levels of HBV transcripts
and replication intermediates as untreated HBV transgenic mice
expressing PPAR
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.
Publication no. 12404-CB from The Scripps Research Institute.
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