A cross-talk between Hepatitis B virus and host mRNAs confers viral adaptation to liver.
A cross-talk between Hepatitis B virus and host mRNAs confers viral adaptation to liver.
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乙型肝炎病毒和宿主 mRNA 之间的串扰赋予病毒对肝脏的适应
DOI：
10.1038/srep10572
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发表时间：
2015-07-17
影响因子：
4.6
通讯作者：
Meng S
中科院分区：
文献类型：
--
作者：
Hu J;Xu Y;Li C;Hao J;Peng S;Chu X;Zhang D;Xu D;Meng S
B型肝炎病毒（HBV）慢性感染全世界约3.5亿人。HBV基因组只有3.2kb，其复制严重依赖宿主因素。先前的研究表明，高表达的肝脏特异性microRNA（miRNA）miR-122以多种方式抑制HBV的表达和复制。在本研究中，我们发现病毒基因组中的miR-122反应元件促进HBV在miR-122高表达的肝细胞中的表达和复制。此外，miR-122应答元件的突变与HBV感染患者的病毒载量和疾病进展相关。接下来，我们通过全基因组表达分析发现，HBV mRNA与miR-122反应元件单独作用可导致多个宿主基因表达改变。HBV mRNA介导的miR-122下调在HBV mRNA诱导的差异基因表达中起主要作用。HBV mRNA可通过降解miR-122和上调其靶细胞周期蛋白G1来增强病毒复制。因此，我们的研究揭示了在HBV感染中高丰度的miR-122和病毒mRNA以及低得多的miR-122靶标水平的独特条件下，HBV可能已经进化为利用miRNA介导的病毒和宿主mRNA网络在肝细胞内实现最佳适应性。
Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide. The replication of HBV which genome is only 3.2 kb long relies heavily on host factors. Previous studies demonstrated that a highly expressed liver-specific microRNA (miRNA) miR-122 suppresses HBV expression and replication in multiple ways. In this study, we found that the miR-122 response elements in viral genome facilitate HBV expression and replication in miR-122 highly-expressed hepatocytes. Moreover, mutations in miR-122 response elements are correlated with viral loads and disease progression in HBV-infected patients. We next found that HBV mRNA with miR-122 response elements alone could lead to altered expression of multiple host genes by whole genome expression analysis. HBV mRNA-mediated miR-122 down-regulation plays a major role in HBV mRNA-induced differential gene expression. HBV mRNA could enhance viral replication via miR-122 degradation and the up-regulation of its target cyclin G1. Our study thereby reveals that under the unique condition of high abundance of miR-122 and viral mRNAs and much lower level of miR-122 target in HBV infection, HBV may have evolved to employ the miRNA-mediated virus and host mRNAs network for optimal fitness within hepatocytes.