Human monoclonal antibody to hepatitis C virus El glycoprotein that blocks virus attachment and viral infectivity
Human monoclonal antibody to hepatitis C virus El glycoprotein that blocks virus attachment and viral infectivity
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DOI：
10.1128/jvi.78.13.7257-7263.2004
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发表时间：
2004-07-01
影响因子：
5.4
通讯作者：
Foung, SKH
中科院分区：
文献类型：
--
作者：
Keck, ZY;Sung, VMH;Foung, SKH
预期响应于丙型肝炎病毒（HCV）感染而引发的人抗体与病毒包膜结构的天然构象反应。将这些抗体分离为阻断病毒结合和进入的人单克隆抗体将可用于提供潜在的治疗试剂和用于疫苗开发。H-111是HCV包膜1蛋白（E1）的抗体，其映射到YEVRNVSGVYH序列并且位于E1的N末端附近，并且能够免疫沉淀E1 E2异源二聚体。H-111与HCV El基因型la、lb、2b和3a的结合表明H-111表位是高度保守的。抗体V区的序列分析显示H-111的体细胞和亲和力成熟的证据。最后，H-111阻断HCV样颗粒与靶细胞的结合和HCV病毒体感染，表明该表位参与病毒结合和进入。
Human antibodies elicited in response to hepatitis C virus (HCV) infection are anticipated to react with the native conformation of the viral envelope structure. Isolation of these antibodies as human monoclonal antibodies that block virus binding and entry will be useful in providing potential therapeutic reagents and for vaccine development. H-111, an antibody to HCV envelope 1 protein (E1) that maps to the YEVRNVSGVYH sequence and is located near the N terminus of El and is able to immunoprecipitate E1E2 heterodimers, is described. Binding of H-111 to HCV El genotypes la, 1b, 2b, and 3a indicates that the H-111 epitope is highly conserved. Sequence analysis of antibody V regions showed evidence of somatic and affinity maturation of H-111. Finally, H-111 blocks HCV-Iike particle binding to and HCV virion infection of target cells, suggesting the involvement of this epitope in virus binding and entry.