TGF-? suppression of HBV RNA through AID-dependent recruitment of an RNA exosome complex.

ABSTRACT: Transforming growth factor (TGF)-? inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-? is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-? was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-? mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-? causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner.

SUBMITTER: Liang G 

PROVIDER: S-EPMC4383551 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other