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PLoS Pathog. 2015 Apr 2;11(4):e1004780. doi: 10.1371/journal.ppat.1004780. eCollection 2015 Apr.

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

Author information

1
Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Department of Microbiology and Immunology, Columbia University, New York, New York, United States of America.
2
Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
3
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.
4
Evolutionary Medicine, Shiga Medical Center Research Institute, Moriyama, Japan.

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.

PMID:
25836330
PMCID:
PMC4383551
DOI:
10.1371/journal.ppat.1004780
[Indexed for MEDLINE]
Free PMC Article

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