TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

PLoS Pathogens

Guangyan Liu¹  Guoxin Liang²  Kouichi Kitamura²  Sajeda Chowdhury²  Masamichi Muramatsu²  Kousho Wakae²  Zhe Wang²  Miki Koura²  Miyuki Shimadu²  Kazuo Kinoshita²  Ahasan Md Monjurul³ 

[1] Department of Microbiology and Immunology, Columbia University, New York, New York, United States of America;Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan;Division of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China

关键词: Small interfering RNAs;    Exosomes;    Nucleocapsids;    Hepatitis B virus;    Immunoprecipitation;    Transfection;    Plasmid construction;    Hepatocytes;   

DOI  :  10.1371/journal.ppat.1004780

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

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