Details

Autor(en) / Beteiligte

• Liang, Guoxin
• Liu, Guangyan
• Kitamura, Kouichi
• Wang, Zhe
• Chowdhury, Sajeda
• Monjurul, Ahasan Md
• Wakae, Kousho
• Koura, Miki
• Shimadu, Miyuki
• Kinoshita, Kazuo
• Muramatsu, Masamichi

Titel

TGF-[beta] suppression of HBV RNA through AID-dependent recruitment of an RNA exosome complex

Ist Teil von

• PLoS pathogens, 2015-04, Vol.11 (4)

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Transforming growth factor (TGF)-[beta] inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-[beta] 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-[beta] was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-[beta] 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-[beta] causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner.