HBV transcription repression in response to genotoxic stress is p53-dependent and abrogated by pX

Transcription of hepatitis B Virus (HBV), an important risk factor of hepat ocellular carcinoma (HCC), is controlled by cellular transcription activato rs including some of the cellular signaling targets, Consequently, HBV tran scription rate changes in response to the cellular physiological conditions . In this report we investigated HBV gene expression and the role of physio logical levels of the viral X protein (pX) under cisplatin induced genotoxi c stress. We show that under these conditions the RNA level of an HBV mutan t which does not express pX is sharply reduced. Studies revealed that trans cription repression is responsible for the observed reduction in HBV RNA le vel. Repression of HBV transcription was obtained only in the p53 proficien t cells. Furthermore, HBV transcription rate is recovered by the cotransfec ted p53 dominant negative plasmid, indicating that p53 is directly responsi ble for HBV transcription repression. Unexpectedly, p73, the recent p53 hom ologue, does not repress but rather activates HBV transcription. Interestin gly, pX produced either by the HBV genome or by a cotransfected plasmid, re lieves the p53 mediated repression. Collectively, these results attribute a physiological role to p53-inactivation by pX, and explain how pX may suppo rt HCC development.