Maillard Patrick, Huby Thierry, Andréo Ursula, Moreau Martine, Chapman John, Budkowska Agata
Hepacivirus Unit, Pasteur Institute, Paris, France.
FASEB J. 2006 Apr;20(6):735-7. doi: 10.1096/fj.05-4728fje. Epub 2006 Feb 13.
The possible role of candidate receptors in the cellular penetration of HCV from serum of infected patients remains unclear. SR-BI/Cla1 interacts with plasma HDL, native and modified LDL, and VLDL, and facilitates cellular cholesterol efflux to lipoprotein acceptors. SR-BI/Cla1 binds HCV E2 protein and interacts with HCV pseudotypes via the HVR1 of the E2 envelope glycoprotein. Our data reveal that functional SR-BI/Cla1 expressed on the surface of CHO cells mediates the binding and uptake of HCV from the sera of infected patients. Interaction between HCV and SR-BI/Cla1 is not sensitive to either anti-E2 or anti-HVR1 antibodies but is effectively inhibited by anti-betalipoprotein antibodies and competed out by apoB-containing lipoproteins and notably by VLDL. We interpret our data to indicate that VLDL associated with or incorporated into HCV plays a critical role in the primary interaction of HCV with SR-BI/Cla1, whereas the HCV E2 protein does not. In addition, our findings in hepatoma cell lines suggest that the interaction of HCV with human hepatocytes is equally mediated, at least in a part, by VLDL, and as such may represent an alternative pathway for infection. The association of HCV with ApoB-containing lipoproteins may promote cellular uptake of this virus in the presence of neutralizing antibodies.
候选受体在丙型肝炎病毒（HCV）从感染患者血清中进行细胞穿透过程中可能发挥的作用仍不清楚。SR-BI/Cla1与血浆高密度脂蛋白（HDL）、天然和修饰的低密度脂蛋白（LDL）以及极低密度脂蛋白（VLDL）相互作用，并促进细胞胆固醇向脂蛋白受体的流出。SR-BI/Cla1结合HCV E2蛋白，并通过E2包膜糖蛋白的高变区1（HVR1）与HCV假型相互作用。我们的数据表明，在CHO细胞表面表达的功能性SR-BI/Cla1介导了从感染患者血清中结合和摄取HCV。HCV与SR-BI/Cla1之间的相互作用对抗E2或抗HVR1抗体均不敏感，但可被抗β脂蛋白抗体有效抑制，并被含载脂蛋白B（apoB）的脂蛋白竞争，尤其是VLDL。我们对数据的解读表明，与HCV相关联或整合入HCV的VLDL在HCV与SR-BI/Cla1的初次相互作用中起关键作用，而HCV E2蛋白并非如此。此外，我们在肝癌细胞系中的研究结果表明，HCV与人肝细胞的相互作用至少部分同样由VLDL介导，因此可能代表一种替代感染途径。在存在中和抗体的情况下，HCV与含apoB脂蛋白的关联可能促进该病毒的细胞摄取。
