Abstract
Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β 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-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β 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-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner.
Highlights
Hepatitis B virus (HBV) is recognized as the major causative factor of severe liver diseases such as cirrhosis and hepatocellular carcinoma
Recent studies have shown that the members of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) deaminase family are antiviral factors that suppress the replication of viruses, such as human immunodeficiency virus type 1 (HIV-1) and HBV
We have demonstrated that Transforming growth factor (TGF)-β1 induces activation-induced cytidine deaminase (AID) expression in hepatocytes, which leads to the downregulation of HBV transcripts and inhibition of nucleocapsid formation
Summary
Hepatitis B virus (HBV) is recognized as the major causative factor of severe liver diseases such as cirrhosis and hepatocellular carcinoma. The clinical outcomes and development of hepatocellular carcinoma and cirrhosis are modulated by viral replication and antiviral immunity against HBV [1]. Two viral proteins (core and P protein) encapsidate pgRNA to form nucleocapsids, where P protein reverse-transcribes pgRNA to produce relaxed circular (RC)-DNA. These nucleocapsids associate with three types of viral surface proteins for secretion as infectious virions [1,2]. The mechanism of HBV replication has been well studied, the mechanisms of antiviral immunity against HBV remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
