Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions
Immunogenic and functional organization of hepatitis C virus (HCV) glycoprotein E2 on infectious HCV virions
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DOI：
10.1128/jvi.01710-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Foung, Steven K. -H.
中科院分区：
文献类型：
--
作者：
Keck, Zhen-Yong;Xia, Jinming;Foung, Steven K. -H.
开发全长丙型肝炎病毒（HCV）RNA有效复制，并在肝癌细胞中产生感染性细胞培养的病毒粒子，HCVRNA，提供了一个机会，以表征病毒包膜蛋白上的免疫原性结构域参与进入靶细胞。一组针对HCV E2糖蛋白上三个免疫原性构象结构域（指定为A、B和C）的免疫球蛋白G1人单克隆抗体（HMAbs）显示，B和C两个结构域内的表位介导HCV-N中和，而针对结构域A的HMAbs均为非中和性。对于结构域B的中和抗体（在不同HCV基因型中具有一些保守表位），使HCV感染降低90%的抑制性抗体浓度，IC 90，范围为0.1至4 μ g/ml。对于一些中和性HMAb，HC 1中和在IC 50和IC 90之间显示出与抗体浓度的线性相关性，而其他显示出非线性相关性。IC 50/IC 90比值与中和HMAb阻断E2与CD 81相互作用的早期发现之间的差异表明，这些抗体阻断病毒-受体相互作用的不同方面。总的来说，这些发现支持HCV E2的免疫原性模型，其具有三个具有不同结构和功能的免疫原性结构域，并为病毒进入所需的CD 81的想法提供了额外的支持。
Development of full-length hepatitis C virus (HCV) RNAs replicating efficiently and producing infectious cell-cultured virions, HCVcc, in hepatoma cells provides an opportunity to characterize immunogenic domains on viral envelope proteins involved in entry into target cells. A panel of immunoglobulin G1 human monoclonal antibodies (HMAbs) to three immunogenic conformational domains (designated A, B, and C) on HCV E2 glycoprotein showed that epitopes within two domains, B and C, mediated HCVcc neutralization, whereas HMAbs to domain A were all nonneutralizing. For the neutralizing antibodies to domain B (with some to conserved epitopes among different HCV genotypes), the inhibitory antibody concentration reducing HCVcc infection by 90%, IC90, ranged from 0.1 to 4 mu g/ml. For some neutralizing HMAbs, HCVcc neutralization displayed a linear correlation with an antibody concentration between the IC50 and the IC90 while others showed a nonlinear correlation. The differences between IC50/IC90 ratios and earlier findings that neutralizing HMAbs block E2 interaction with CD81 suggest that these antibodies block different facets of virus-receptor interaction. Collectively, these findings support an immunogenic model of HCV E2 having three immunogenic domains with distinct structures and functions and provide added support for the idea that CD81 is required for virus entry.