In vivo regulation of hepatitis B virus replication by peroxisome proliferators

The role of the peroxisome proliferator-activated receptor alpha (PPAR alph a) in regulating hepatitis B virus (HBV) transcription and replication in v ivo was investigated in an HBV transgenic mouse model. Treatment of HBV tra nsgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and st eady-state levels of HBV RNAs in the livers of these mice. In male mice, th is 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 increase s in transcription and replication were dependent on PPARa. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV tra nscripts and replication intermediates as untreated HBV transgenic mice exp ressing PPAR alpha but failed to demonstrate alterations in either RNA or D NA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumsta nces, result in relatively large increases in HBV replication in HBV transg enic mice.