The Effect Of HNF3 Binding Site Mutation In The Inhibition Role Of Hepatocyte Nuclear Factor 3β On HBV Transcription And Replication

ObjectiveThe liver-enriched transcription factors are a class of protein molecules with function of genetic transcription in the liver. It was showed that the liver-enriched transcription factors can bind to the four promoters of HBV and modulate the HBV transcription. Among them,the liver-enriched nuclear hormone receptors ,HNF4 and RXR α plus PPAR α ,can support HBV transcription and replication in nonhepatoma cell line. It is also showed that the nuclear hormone receptor-mediated viral replication was negatively regulated by HNF3. In order to understand transcriptional regulation of HBV by HNF3, HBV recombinant plasmids were constructed, with multi-mutations of HNF3 binding sites , which were in HBV polymerase open reading frame, PS1 promoter or S promoter. By inhibiting HNF3 to bind to HNF3 binding sites in HBV genome, it may show whether HNF3 β can inhibit the HBV transcription and replication .So the key target was found, with which hepatocyte nuclear factor 3 can inhibits HBV transcription and replication. Methods1.To construct the multi-mutant pHBV4.1HNF3 mut plasmids, three...