Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes.
Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes.
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DOI：
10.1002/hep.24523
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发表时间：
2011-10
期刊：
影响因子：
13.5
通讯作者：
Ray, Ranjit
中科院分区：
文献类型：
--
作者：
Mazumdar, Budhaditya;Banerjee, Arup;Meyer, Keith;Ray, Ranjit
我们以前的研究表明，丙型肝炎病毒（HCV）的包膜糖蛋白，E1和E2，显示不同的细胞表面分子的反应性。在这项研究中，我们的特点是E1和E2与载脂蛋白的相互作用，促进病毒进入。结果表明，载脂蛋白E（ApoE）抗体对VSV/HCV E1-G假型感染的中和作用高于载脂蛋白B（ApoB），VSV/HCV E2-G假型感染基本不受影响。通过ApoE抗血清中和细胞培养物生长的HCV感染性，并在较小程度上通过ApoB中和，进一步证实了它们参与病毒进入。通过ELISA，HCV E1而不是E2显示与ApoE和ApoB结合。E1与载脂蛋白的结合得到了来自表达E1的人肝细胞的免疫共沉淀的进一步支持。所选E1胞外域衍生肽的兔抗血清显示约50%的E1-G假型感染性中和。此外，E1胞外域衍生的合成肽显着抑制E1与载脂蛋白的相互作用。对LDL-R作为肝细胞表面受体在病毒进入中的作用的研究表明，通过使用人前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK 9）和血小板因子-4（PF 4）抑制LDL-R配体结合活性，可显著减少E1-G假型空斑数量（约70%），而它们对E2-G假型的抑制作用极小。总之，结果表明HCV E1和载脂蛋白之间存在关联，这可能有助于病毒通过LDL-R进入哺乳动物细胞。
Our previous studies demonstrated that hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, display distinct reactivity to different cell surface molecules. In this study, we characterized the interaction of E1 and E2 with apolipoproteins in facilitating virus entry. The results suggested a higher neutralization of VSV/HCV E1-G pseudotype infectivity by antibodies to apolipoprotein E (ApoE) than apolipoprotein B (ApoB), with VSV/HCV E2-G pseudotype infectivity remaining largely unaffected. Neutralization of cell culture grown HCV infectivity by antiserum to ApoE, and to a lesser extent by ApoB, further verified their involvement in virus entry. HCV E1, but not E2, displayed binding with ApoE and ApoB by ELISA. Binding of E1 with apolipoproteins were further supported by coimmunoprecipitation from human hepatocytes expressing E1. Rabbit antiserum to a selected E1 ectodomain derived peptide displayed ~50% neutralization of E1-G pseudotype infectivity. Furthermore, E1 ectodomain derived synthetic peptides significantly inhibited the interaction of E1 with both the apolipoproteins. Investigation on the role of LDL-R as a hepatocyte surface receptor for virus entry suggested a significant reduction in E1-G pseudotype plaque numbers (~70%) by inhibiting LDL-R ligand binding activity using human proprotein convertase subtilisin/kexin type 9 (PCSK9) and platelet factor-4 (PF4), while they had a minimal inhibitory effect on E2-G pseudotype. Together, the results suggested an association between HCV E1 and apolipoproteins, which may facilitate virus entry through LDL-R into mammalian cells.
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