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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structural basis for the antibody neutralization of Herpes simplex virus
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Structural basis for the antibody neutralization of Herpes simplex virus

机译：抗体中和结构依据单纯疱疹病毒

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Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD-nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.
机译：糖蛋白D (gD)的单纯疱疹病毒(HSV)与宿主细胞表面受体结合,需要触发病毒膜融合进入宿主细胞。验证anti-HSV治疗的目标抗体的发展。单克隆抗体E317 (mAb E317)以前提高了病毒对HSV gD中和。基于抗体中和,晶体的gD ectodomain绑定到E317外事局域获得的。主要通过,E317与gD重链,幅员辽阔抗原决定基认识gD,灵活氨基和c端构象。抗原决定基核心结构映射到外部gD表面,对应绑定的网站两种受体,疱疹病毒条目中保(HVEM)和nectin-1调解HSV感染。gD-nectin-1 E317直接承认接口和阻塞的HVEM联系网站gD受体阻断其绑定。结合E317 gD也禁止gD的氨基端发夹的形成HVEM认可。gD与nectin-1-binding残留或中和抗原网站确定到目前为止(Tyr38 Asp215 Arg222和Phe223)。两种类型的人类之间高度保守的疱疹病毒(1型单纯疱疹病毒和HSV-2)。相关的virus-neutralizing抗原表位与受体结合区域。进一步加强前面了治疗和诊断E317的潜力抗体

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