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鉴定靶向寨卡病毒包膜蛋白糖环的两种高特异性单克隆抗体。

Characterization of Two Highly Specific Monoclonal Antibodies Targeting the Glycan Loop of the Zika Virus Envelope Protein.

机构信息

Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawai'i, Honolulu, Hawai'i, USA.

Microbiology and Biotechnology, Math/Science Department, Kapiolani Community College, University of Hawai'i, Honolulu, Hawai'i, USA.

出版信息

Viral Immunol. 2024 Apr;37(3):167-175. doi: 10.1089/vim.2023.0153. Epub 2024 Apr 4.

Abstract

Zika virus (ZIKV) is an emerging flavivirus associated with several neurological diseases such as Guillain-Barré syndrome in adults and microcephaly in newborn children. Its distribution and mode of transmission (via and mosquitoes) collectively cause ZIKV to be a serious concern for global health. High genetic homology of flaviviruses and shared ecology is a hurdle for accurate detection. Distinguishing infections caused by different viruses based on serological recognition can be misleading as many anti-flavivirus monoclonal antibodies (mAbs) discovered to date are highly cross-reactive, especially those against the envelope (E) protein. To provide more specific research tools, we produced ZIKV E directed hybridoma cell lines and characterized two highly ZIKV-specific mAb clones (mAbs A11 and A42) against several members of the genus. Epitope mapping of mAb A11 revealed glycan loop specificity in Domain I of the ZIKV E protein. The development of two highly specific mAbs targeting the surface fusion protein of ZIKV presents a significant advancement in research capabilities as these can be employed as essential tools to enhance our understanding of ZIKV identification on infected cells or in culture.

摘要

Zika 病毒(ZIKV)是一种新兴的黄病毒,与几种神经系统疾病有关,如成人中的格林-巴利综合征和新生儿中的小头畸形。其分布和传播方式(通过 和 蚊子)共同导致 ZIKV 成为全球健康的严重关注点。黄病毒的高遗传同源性和共同的生态是准确检测的一个障碍。基于血清学识别来区分由不同病毒引起的感染可能会产生误导,因为迄今为止发现的许多抗黄病毒单克隆抗体(mAbs)高度交叉反应,尤其是针对包膜(E)蛋白的 mAbs。为了提供更具特异性的研究工具,我们生产了针对 ZIKV E 蛋白的杂交瘤细胞系,并对针对 属的几个成员的两种高度特异性的 mAb 克隆(mAbs A11 和 A42)进行了表征。mAb A11 的表位作图显示了 ZIKV E 蛋白结构域 I 中的糖环特异性。针对 ZIKV 表面融合蛋白的两种高度特异性 mAb 的开发是研究能力的重大进步,因为这些 mAb 可以作为重要工具,增强我们对感染细胞或培养物中 ZIKV 鉴定的理解。

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本文引用的文献

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Zika Virus Structure, Maturation, and Receptors.寨卡病毒结构、成熟和受体。
J Infect Dis. 2017 Dec 16;216(suppl_10):S935-S944. doi: 10.1093/infdis/jix515.
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A novel mechanism of antibody-mediated enhancement of flavivirus infection.抗体介导增强黄病毒感染的一种新机制。
PLoS Pathog. 2017 Sep 15;13(9):e1006643. doi: 10.1371/journal.ppat.1006643. eCollection 2017 Sep.
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A guinea pig model of Zika virus infection.寨卡病毒感染的豚鼠模型
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