A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses
A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses
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DOI：
10.1002/hep.28013
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发表时间：
2016-01-01
期刊：
影响因子：
13.5
通讯作者：
Baumert, Thomas F.
中科院分区：
文献类型：
--
作者：
Verrier, Eloi R.;Colpitts, Che C.;Baumert, Thomas F.
慢性乙肝和丁型肝炎是世界范围内肝脏疾病和肝细胞癌的主要原因。缺乏有效的治愈方法。乙肝病毒和丁型肝炎病毒共享相同的包膜蛋白，它们使用钠/牛磺胆酸盐共转运多肽(一种胆汁酸转运体)作为受体进入肝细胞。然而，病毒进入过程的详细机制仍然知之甚少。在这里，我们建立了一个高通量的感染细胞培养模型，使丁型肝炎病毒进入和感染的功能基因组学成为可能。使用靶向RNA干扰进入筛选，我们确定Glypican5是乙肝和德尔塔病毒的共同宿主细胞进入因子。结论：这些发现促进了我们对病毒细胞进入的理解，并为治疗开辟了新的途径。由于Glypicans已被证明在控制细胞分裂和生长调节中发挥作用，病毒与Glypican5的相互作用也可能在病毒诱导的肝病和癌症的发病机制中发挥作用。(《肝病》2016；63：35-48)
Chronic hepatitis B and D infections are major causes of liver disease and hepatocellular carcinoma worldwide. Efficient therapeutic approaches for cure are absent. Sharing the same envelope proteins, hepatitis B virus and hepatitis delta virus use the sodium/taurocholate cotransporting polypeptide (a bile acid transporter) as a receptor to enter hepatocytes. However, the detailed mechanisms of the viral entry process are still poorly understood. Here, we established a high-throughput infectious cell culture model enabling functional genomics of hepatitis delta virus entry and infection. Using a targeted RNA interference entry screen, we identified glypican 5 as a common host cell entry factor for hepatitis B and delta viruses. Conclusion: These findings advance our understanding of virus cell entry and open new avenues for curative therapies. As glypicans have been shown to play a role in the control of cell division and growth regulation, virus-glypican 5 interactions may also play a role in the pathogenesis of virus-induced liver disease and cancer. (Hepatology 2016;63:35-48)