HIV Vpr protein upregulates microRNA-122 expression and stimulates hepatitis C virus replication.
HIV Vpr protein upregulates microRNA-122 expression and stimulates hepatitis C virus replication.
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HIV Vpr 蛋白上调 microRNA-122 表达并刺激丙型肝炎病毒复制
DOI：
10.1099/vir.0.000169
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发表时间：
2015-08
期刊：
影响因子：
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通讯作者：
Gong G
中科院分区：
文献类型：
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作者：
Peng M;Xiao X;He Y;Jiang Y;Zhang M;Peng F;Tian Y;Xu Y;Gong G
人类免疫缺陷病毒（HIV）/丙型肝炎病毒（HCV）合并感染的特点是血清HCV RNA载量高于HCV单一感染。然而，HIV和HCV复制之间的关系仍有待澄清。HIV Vpr已被证明在HIV复制中发挥重要作用。本研究旨在探讨Vpr在HCV复制和发病机制中的作用。因此，我们使用基因型2a全长HCV株JFH 1感染系统和基因型1b全长HCV复制子OR 6细胞系来分析Vpr对HCV复制的影响。在两种HCV感染细胞模型中发现Vpr可促进HCV 5′ UTR活性、HCVRNA复制和HCV蛋白表达。此外，淋巴细胞产生的Vpr显著诱导HCV 5′ UTR活性和HCV在肝细胞中的复制。我们还发现Vpr通过刺激miR-122的启动子活性而上调其表达。此外，miR-122抑制剂抑制了Vpr介导的HCV 5′ UTR活性和HCV复制的增强。综上所述，我们的研究结果表明Vpr上调miR-122的表达与Vpr刺激HCV 5′ UTR活性和HCV复制密切相关，为HIV/HCV共感染过程中HIV与HCV的相互作用提供了新的证据。
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection is characterized by higher serum HCV RNA loads compared with HCV mono-infection. However, the relationship between HIV and HCV replication remains to be clarified. HIV Vpr has been shown to play an essential role in HIV replication. In this study, we aimed to explore the role of Vpr in HCV replication and pathogenesis. We therefore used the genotype 2a full-length HCV strain JFH1 infection system and the genotype 1b full-length HCV replicon OR6 cell line to analyse the effects of Vpr on HCV replication. We found that Vpr promoted HCV 5′ UTR activity, HCV RNA replication and HCV protein expression in two HCV infection cell models. Additionally, lymphocyte-produced Vpr significantly induced HCV 5′ UTR activity and HCV replication in hepatocytes. We also found that Vpr upregulated the expression of miR-122 by stimulating its promoter activity. Furthermore, an miR-122 inhibitor suppressed the Vpr-mediated enhancement of both HCV 5′ UTR activity and HCV replication. In summary, our results revealed that the Vpr-upregulated expression of miR-122 is closely related to the stimulation of HCV 5′ UTR activity and HCV replication by Vpr, providing new evidence for how HIV interacts with HCV during HIV/HCV co-infection.