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登革病毒包膜蛋白结构域 III 诱导的抗体在小鼠模型中对寨卡病毒起到交叉保护作用。

Dengue virus envelope protein domain III-elicited antibodies mediate cross-protection against Zika virus in a mouse model.

机构信息

Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.

Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; The Sixth People's Hospital of Wenzhou, Wenzhou, Zhejiang, 325000, China.

出版信息

Virus Res. 2020 Mar;278:197882. doi: 10.1016/j.virusres.2020.197882. Epub 2020 Jan 22.

Abstract

Dengue virus (DENV) and Zika virus (ZIKV) are antigenically related mosquito-transmitted viruses which represent a big public health problem. Although the antigenic cross-reactivity between two viruses were intensively investigated at the antibody and T cell levels, how DENV envelope protein domain III (EDIII)-elicited antibodies (Abs) impact the outcome of ZIKV infection is uncertain. Here, our results show that the sera isolated from DENV-EDIII-immunized wild-type mice recognized ZIKV-EDIII and cross-neutralized ZIKV in vitro. Passive transfer of DENV-EDIII-immune sera protected 1-day-old mice against lethal ZIKV challenge. Finally, maternally acquired anti-DENV-EDIII Abs significantly increased the survival of 1-day-old mice born to DENV-EDIII-immunized mothers post ZIKV challenge. These results reveal that DENV-EDIII-induced Abs provide cross-protection against ZIKV and may not mediate the Ab-dependent enhancement of ZIKV infection at the concentration used here. The present study would contribute to the development and application of DENV-EDIII-based vaccines.

摘要

登革热病毒(DENV)和寨卡病毒(ZIKV)是具有抗原相关性的经蚊传播病毒,它们是一个严重的公共卫生问题。尽管在抗体和 T 细胞水平上对两种病毒的抗原交叉反应性进行了深入研究,但 DENV 包膜蛋白结构域 III(EDIII)诱导的抗体(Abs)如何影响 ZIKV 感染的结果尚不确定。在这里,我们的研究结果表明,从 DENV-EDIII 免疫野生型小鼠中分离的血清可识别 ZIKV-EDIII 并在体外中和 ZIKV。DENV-EDIII 免疫血清的被动转移可保护 1 日龄小鼠免受致死性 ZIKV 攻击。最后,母体获得的抗 DENV-EDIII Abs 显著增加了在 ZIKV 攻击后出生于 DENV-EDIII 免疫母亲的 1 日龄小鼠的存活率。这些结果表明,DENV-EDIII 诱导的 Abs 提供了针对 ZIKV 的交叉保护作用,并且在使用的浓度下可能不会介导 Ab 依赖性增强 ZIKV 感染。本研究将有助于 DENV-EDIII 为基础的疫苗的开发和应用。

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