Herpes simplex virus 1 envelope glycoprotein C shields glycoprotein D to protect virions from entry-blocking antibodies.

IF 4 2区 医学 Q2 VIROLOGY
McKenna A Hull, Suzanne M Pritchard, Anthony V Nicola
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引用次数: 0

Abstract

Herpes simplex virus 1 (HSV-1) gD interaction with the host cell receptor nectin-1 triggers the membrane fusion cascade during viral entry. Potent neutralizing antibodies to gD prevent receptor-binding or prevent gD interaction with gH/gL critical for fusion. HSV has many strategies to evade host immune responses. We investigated the ability of virion envelope gC to protect envelope gD from antibody neutralization. HSV-1 lacking gC was more sensitive to neutralization by anti-gD monoclonal antibodies than a wild-type rescuant virus. gD in the HSV-1 gC-null viral envelope had enhanced reactivity to anti-gD antibodies compared to wild type. Soluble nectin-1 bound similar to HSV-1 particles regardless of the presence of gC in the envelope. However, entry of HSV-1 ΔgC was more sensitive to inhibition by soluble nectin-1 receptor. The viral membrane protein composition of HSV-1 ΔgC is equivalent to that of wild type, suggesting that the lack of gC is responsible for the increased reactivity of gD-specific antibodies and the consequent increased susceptibility to neutralization by those antibodies. Together, the results suggest that gC in the HSV-1 envelope shields both receptor-binding domains and gH/gL-interacting domains of gD from neutralizing antibodies, facilitating HSV cell entry.IMPORTANCEHSV-1 causes lifelong infections. There is no vaccine and no cure. Understanding HSV immune evasion strategies is an important goal. HSV-1 gC is a multi-functional envelope glycoprotein. This study suggests that virion gC physically shields neighboring gD from antibodies, including neutralizing monoclonal antibodies. This mechanism may allow HSV to escape immune detection, promoting HSV infection in the host.

单纯疱疹病毒1型包膜糖蛋白C屏蔽糖蛋白D,保护病毒粒子免受进入阻断抗体的侵害。
单纯疱疹病毒1型(HSV-1) gD与宿主细胞受体连接素-1的相互作用在病毒进入时触发膜融合级联反应。有效的gD中和抗体阻止受体结合或阻止gD与融合关键的gH/gL相互作用。HSV有许多逃避宿主免疫反应的策略。我们研究了病毒粒子包膜gC保护包膜gD免受抗体中和的能力。缺乏gC的HSV-1比野生型救援病毒对抗gd单克隆抗体的中和更敏感。与野生型相比,HSV-1 gC-null病毒包膜中的gD对抗gD抗体的反应性增强。可溶性连接蛋白-1与HSV-1颗粒结合相似,而不管包膜中是否存在gC。然而,HSV-1 ΔgC的进入对可溶性连接素-1受体的抑制更为敏感。HSV-1 ΔgC的病毒膜蛋白组成与野生型相当,这表明gC的缺乏导致了gd特异性抗体的反应性增加,从而增加了对这些抗体的中和敏感性。综上所述,结果表明HSV-1包膜中的gC屏蔽了gD的受体结合域和gH/ gl相互作用域,使其免受中和抗体的影响,从而促进HSV细胞进入。hsv -1可导致终身感染。没有疫苗和治疗方法。了解HSV免疫逃避策略是一个重要的目标。HSV-1 gC是一种多功能包膜糖蛋白。该研究表明,gC病毒粒子可以物理地屏蔽邻近gD的抗体,包括中和性单克隆抗体。这一机制可能使HSV逃避免疫检测,促进宿主的HSV感染。
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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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