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两种耐药机制的结合对于蜱传脑炎病毒逃避广泛中和的人类抗体至关重要。

A combination of two resistance mechanisms is critical for tick-borne encephalitis virus escape from a broadly neutralizing human antibody.

机构信息

Veterinary Research Institute, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Ceske Budejovice, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic; Department of Pharmacology and Pharmacy, Faculty of Veterinary Medicine, University of Veterinary Sciences, Brno, Czech Republic.

Veterinary Research Institute, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.

出版信息

Cell Rep. 2023 Sep 26;42(9):113149. doi: 10.1016/j.celrep.2023.113149. Epub 2023 Sep 19.

DOI:10.1016/j.celrep.2023.113149
PMID:37715951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10591882/
Abstract

Tick-borne encephalitis virus (TBEV) is a flavivirus that causes human neuroinfections and represents a growing health problem. The human monoclonal antibody T025 targets envelope protein domain III (EDIII) of TBEV and related tick-borne flaviviruses, potently neutralizing TBEV in vitro and in preclinical models, representing a promising candidate for clinical development. We demonstrate that TBEV escape in the presence of T025 or T028 (another EDIII-targeting human monoclonal antibody) results in virus variants of reduced pathogenicity, characterized by distinct sets of amino acid changes in EDII and EDIII that are jointly needed to confer resistance. EDIII substitution K311N impairs formation of a salt bridge critical for T025-epitope interaction. EDII substitution E230K is not on the T025 epitope but likely induces quaternary rearrangements of the virus surface because of repulsion of positively charged residues on the adjacent EDI. A combination of T025 and T028 prevents virus escape and improves neutralization.

摘要

蜱传脑炎病毒（TBEV）是一种黄病毒，可引起人类神经感染，是一个日益严重的健康问题。人类单克隆抗体 T025 靶向 TBEV 及相关蜱传黄病毒的包膜蛋白结构域 III（EDIII），在体外和临床前模型中具有强大的中和 TBEV 的作用，是一种很有前途的临床开发候选药物。我们证明，TBEV 在 T025 或 T028（另一种靶向 EDIII 的人类单克隆抗体）存在的情况下发生逃逸，会导致病毒毒力降低的变异株，其特征是在 EDII 和 EDIII 中存在不同的氨基酸变化组合，这些变化共同赋予了病毒对 T025 的耐药性。EDIII 取代 K311N 会破坏对 T025 表位相互作用至关重要的盐桥形成。EDII 取代 E230K 不在 T025 表位上，但由于相邻 EDI 上带正电荷的残基的排斥，可能会诱导病毒表面的四级重排。T025 和 T028 的联合使用可以防止病毒逃逸并提高中和效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e52/10591882/7f036ea0d223/nihms-1933926-f0006.jpg
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本文引用的文献

1
Tick-borne encephalitis: A comprehensive review of the epidemiology, virology, and clinical picture.蜱传脑炎：流行病学、病毒学和临床特征的综合综述。
Rev Med Virol. 2023 Sep;33(5):e2470. doi: 10.1002/rmv.2470. Epub 2023 Jul 1.
2
Changes to virus taxonomy and the ICTV Statutes ratified by the International Committee on Taxonomy of Viruses (2023).病毒分类学的变化和国际病毒分类学委员会（ICTV）章程的修订（2023 年）。
Arch Virol. 2023 Jun 10;168(7):175. doi: 10.1007/s00705-023-05797-4.
3
New directions in the experimental therapy of tick-borne encephalitis.
Structural diversity of tick-borne encephalitis virus particles in the inactivated vaccine based on strain Sofjin.
基于索非亚株的灭活疫苗中蜱传脑炎病毒颗粒的结构多样性
Emerg Microbes Infect. 2024 Dec;13(1):2290833. doi: 10.1080/22221751.2023.2290833. Epub 2024 Mar 11.
4
Tick-Borne Encephalitis (TBE): From Tick to Pathology.蜱传脑炎（TBE）：从蜱虫到病理变化
J Clin Med. 2023 Oct 30;12(21):6859. doi: 10.3390/jcm12216859.
蜱传脑炎实验性治疗的新方向
Antiviral Res. 2023 Feb;210:105504. doi: 10.1016/j.antiviral.2022.105504. Epub 2022 Dec 24.
4
Therapeutic monoclonal antibodies for COVID-19 management: an update.治疗 COVID-19 的单克隆抗体：最新进展。
Expert Opin Biol Ther. 2022 Jun;22(6):763-780. doi: 10.1080/14712598.2022.2078160. Epub 2022 May 29.
5
Molecular Organisation of Tick-Borne Encephalitis Virus.蜱传脑炎病毒的分子结构
Viruses. 2022 Apr 11;14(4):792. doi: 10.3390/v14040792.
6
Neutralizing antibody: a savior in the Covid-19 disease.中和抗体：Covid-19 疾病的救星。
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7
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8
Autochthonous tick-borne encephalitis in the United Kingdom: A second probable human case and local eco-epidemiological findings.英国本土蜱传脑炎：第二例可能的人类病例及局部生态流行病学发现。
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9
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J Exp Med. 2021 May 3;218(5). doi: 10.1084/jem.20210236.