Keck Zhen-Yong, Xia Jinming, Cai Zhaohui, Li Ta-Kai, Owsianka Ania M, Patel Arvind H, Luo Guangxiang, Foung Steven K H
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
J Virol. 2007 Jan;81(2):1043-7. doi: 10.1128/JVI.01710-06. Epub 2006 Nov 1.
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 microg/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.
全长丙型肝炎病毒（HCV）RNA在肝癌细胞中高效复制并产生感染性细胞培养病毒颗粒（HCVcc），这为鉴定病毒包膜蛋白上参与进入靶细胞的免疫原性结构域提供了机会。一组针对HCV E2糖蛋白上三个免疫原性构象结构域（分别命名为A、B和C）的免疫球蛋白G1人单克隆抗体（HMAbs）显示，B和C这两个结构域内的表位介导了HCVcc的中和作用，而针对结构域A的HMAbs均无中和作用。对于针对结构域B的中和抗体（其中一些针对不同HCV基因型中的保守表位），使HCVcc感染减少90%的抑制性抗体浓度（IC90）范围为0.1至4微克/毫升。对于一些中和性HMAbs，HCVcc中和作用与IC50和IC90之间的抗体浓度呈线性相关，而其他一些则呈非线性相关。IC50/IC90比值与早期发现的中和性HMAbs阻断E2与CD81相互作用之间的差异表明，这些抗体阻断病毒 - 受体相互作用的不同方面。总体而言，这些发现支持HCV E2具有三个具有不同结构和功能的免疫原性结构域的免疫原性模型，并为CD81是病毒进入所必需的这一观点提供了更多支持。
