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肠道病毒中和作用的结构基础。

Structural basis for neutralization of enterovirus.

机构信息

Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.

出版信息

Curr Opin Virol. 2021 Dec;51:199-206. doi: 10.1016/j.coviro.2021.10.006. Epub 2021 Nov 5.

Abstract

Outbreaks of enteroviral infections are associated with morbidity and mortality in susceptible individuals worldwide. There are still no antiviral drugs or vaccines against most circulating enteroviruses. Antibody-mediated immunity is crucial for preventing and limiting enteroviral infections. In this review, we focus on enteroviruses that continue to cause endemics in recent years, such as rhinovirus, enterovirus A71, coxsackievirus, and echovirus, and introduce a structural understanding of the mechanisms of virus neutralization. The mechanisms by which virus-specific antibodies neutralize enteroviruses have been explored not only through study of viral structures, but also through understanding virus-antibody interactions at the amino acid level. Neutralizing epitopes are predominantly mapped on the canyon northern rim, canyon inner surface, canyon southern rim, and twofold and threefold plateaus of the capsid, where surface-exposed loops are located. This review also describes recent progress in deciphering the virus-receptor complex and structural rearrangements involved in the uncoating process, providing insight into plausible virus neutralization mechanisms.

摘要

肠道病毒感染的爆发与全球易感人群的发病率和死亡率有关。目前仍没有针对大多数循环肠道病毒的抗病毒药物或疫苗。抗体介导的免疫对于预防和限制肠道病毒感染至关重要。在这篇综述中,我们重点关注近年来仍持续流行的肠道病毒,如鼻病毒、肠道病毒 A71、柯萨奇病毒和埃可病毒,并介绍病毒中和机制的结构理解。病毒特异性抗体中和肠道病毒的机制不仅通过研究病毒结构进行了探索,还通过在氨基酸水平上理解病毒-抗体相互作用进行了探索。中和表位主要映射在衣壳的峡谷北部边缘、峡谷内表面、峡谷南部边缘、以及二倍和三倍高原上,这些位置都有位于表面暴露环。这篇综述还描述了最近在破译病毒-受体复合物和解开衣壳脱壳过程中涉及的结构重排方面的进展,为合理的病毒中和机制提供了见解。

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