The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus
The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus
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DOI：
10.1093/emboj/cdf529
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发表时间：
2002-10-01
期刊：
影响因子：
11.4
通讯作者：
Vitelli, A
中科院分区：
文献类型：
--
作者：
Scarselli, E;Ansuini, H;Vitelli, A
我们发现丙型肝炎病毒（HCV）包膜糖蛋白E2与人肝癌细胞系的结合不依赖于先前提出的HCV受体CD 81。使用来自最流行的Ia和Ib基因型的重组E2的比较结合研究显示，肝癌细胞对E2的识别独立于病毒分离株，而E2-CD 81相互作用是分离株特异性的。可溶性E2与人肝癌细胞的结合因高变区1（HVR 1）的缺失而受损，但野生型表型通过引入先前报道的补偿突变来恢复，以挽救HVR 1缺失的HCV感染性克隆的感染性。我们已经确定负责E2结合到人肝细胞的受体作为人清道夫受体B类I型（SR-BI）。E2-SR-BI相互作用是非常选择性的，因为小鼠SR-BI和密切相关的人清道夫受体CD 36都不能结合E2。最后，E2的识别SR-BI的竞争在一个孤立的具体方式在肝癌细胞系和人SR-BI转染细胞系的抗HVR 1单克隆抗体。
We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent la and 1b genotypes revealed that E2 recognition by hepatoma cells is independent from the viral isolate, while E2-CD81 interaction is isolate specific. Binding of soluble E2 to human hepatoma cells was impaired by deletion of the hypervariable region 1 (HVR1), but the wild-type phenotype was recovered by introducing a compensatory mutation reported previously to rescue infectivity of an HVR1-deleted HCV infectious clone. We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR-BI). E2-SR-BI interaction is very selective since neither mouse SR-BI nor the closely related human scavenger receptor CD36, were able to bind E2. Finally, E2 recognition by SR-BI was competed out in an isolate-specific manner both on the hepatoma cell line and on the human SR-BI-transfected cell line by an anti-HVR1 monoclonal antibody.