Que Lusheng, Liu Guangyan, Kitamura Kouichi, Wakae Kousho, Li Yingfang, Nishitsuji Hironori, Ujino Saneyuki, Shimotohno Kunitada, Muramatsu Masamichi
Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan; Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Virology. 2017 Oct;510:281-288. doi: 10.1016/j.virol.2017.07.035. Epub 2017 Aug 2.
Hepatitis B virus (HBV) is the major cause of liver cirrhosis and hepatocellular carcinoma. After entering a hepatocyte, HBV forms a nuclear viral episome and produces pregenomic (pg) RNA with a stem-loop structure called an epsilon, which acts to signal encapsidation. We previously demonstrated that TGF-β upregulates activation-induced cytidine deaminase (AID) expression in hepatocytes, which in turn downregulates HBV transcripts by recruiting the RNA exosome complex. The molecular mechanism underlying AID-mediated HBV RNA reduction remains largely unclear. Here we used a pgRNA reporter system having a reporter gene within pgRNA to identify sis- and trans-acting elements in AID-mediated HBV RNA reduction. We found that the epsilon RNA and C-terminus of AID are required for AID-mediated HBV RNA reduction. Importantly, this reduction was reproduced in a hydrodynamic HBV transfection mouse model. The molecular mechanism of AID-mediated HBV RNA reduction is discussed.
乙型肝炎病毒（HBV）是肝硬化和肝细胞癌的主要病因。进入肝细胞后，HBV形成核病毒附加体并产生具有称为ε的茎环结构的前基因组（pg）RNA，该结构用于信号包装。我们先前证明，转化生长因子-β（TGF-β）上调肝细胞中激活诱导的胞苷脱氨酶（AID）的表达，进而通过募集RNA外泌体复合物来下调HBV转录本。AID介导的HBV RNA减少的分子机制在很大程度上仍不清楚。在这里，我们使用了一个在pgRNA中具有报告基因的pgRNA报告系统，以鉴定AID介导的HBV RNA减少中的顺式和反式作用元件。我们发现，AID介导的HBV RNA减少需要εRNA和AID的C末端。重要的是，这种减少在水动力HBV转染小鼠模型中得到了重现。本文讨论了AID介导的HBV RNA减少的分子机制。
