Plos pathogens:TGFβ抑制乙型肝炎病毒复制机制

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近日，国际学术期刊plos pathogens在线发表了日本科学家的一项最新研究进展，他们发现在TGFβ对乙型肝炎病毒（HBV）复制的抑制过程依赖于活化诱导胞嘧啶核苷脱氨酶（AID）的表达，AID能够显著抑制HBV转录和病毒DNA合成，最终导致对病毒复制的抑制。


乙型肝炎病毒（HBV）是导致肝细胞癌发生的一个重要诱发因素。TGFβ能够抑制乙型肝炎病毒（HBV）复制，但对于参与该过程的细胞内效应因子了解甚少。通过实验发现AID能够与病毒P蛋白发生相互作用结合病毒特定的RNA序列。AID还可以与一种RNA降解复合物（RNA exosome）发生结合，这表明AID，RNA exosome和P蛋白能够形成RNP复合物。删除AID或RNA exosome能够消除TGFβ对HBV转录的抑制，因此，AID和RNA exosome参与了TGFβ介导的对HBV RNA转录的抑制。研究人员进一步证明，当P蛋白表达受到影响或病毒转录受到抑制，AID介导的HBV下降就不会发生。

综上所述，这些结果表明通过TGFβ诱导AID表达会引起对RNA exosome的招募形成RNP复合物，RNA exosome能够通过与转录偶联的方式降解HBV RNA，从而发挥抗HBV的功能。

[size=16.3636360168457px]http://news.bioon.com/article/6667765.html

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

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

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.

http://journals.plos.org/plospat ... ournal.ppat.1004780