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Updated: Jun 2, 2025

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors

Published on: September 13, 2018

转移受体识别的分子基础由脑性树冠病毒

Xiaoyi Fan¹, Wanyu Li¹, Jessica Oros¹

¹Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

bioRxiv : the preprint server for biology

|January 13, 2025

概括

西方马类脑炎病毒 (WEEV) 重新出现,其尖端蛋白的遗传变化改变了受体结合. 这解释了WEEV毒性和宿主适应性的转变,影响了疫情的准备.

科学领域:

病毒学病毒学
结构生物学结构生物学
流行病学流行病学

背景情况:

西部马类脑炎病毒 (WEEV) 在南美洲重新出现,导致人类和马类严重爆发.
韦氏病毒利用原cadherin 10 (PCDH10) 作为主要受体,但受体结合在病原性和非病原性菌株之间有所不同.
病毒性WEEV菌株也可以使用非常低密度脂蛋白受体 (VLDLR) 和阿波利波蛋白E受体2 (ApoER2) 作为替代受体.

研究的目的:

阐明WEEV转移受体依赖性的结构基础.
了解WEEV遗传多态性如何影响神经毒性和宿主热带性.
为了告知arbovirus爆发的准备情况,并提高对病毒病原学的理解.

主要方法:

使用冷电子显微镜来确定与哺乳动物受体结合的WEEV菌株的结构.
对WEEV尖蛋白多态性的分析.
预测额外WEEV和相关的alphavirus菌株的受体依赖性.

主要成果:

结构分析确定了WEEV尖端蛋白与受体结合改变相关的关键多态性.
这些多态性解释了从旧菌株的PCDH10依赖转向新兴菌株中更广泛的受体使用的转变.
具有特定多形态的非致病菌株可以通过利用替代受体感染主要皮质神经元.

结论:

在WEEV尖端蛋白中的病毒多态性是受体热带性和神经病毒性的关键驱动因素.
了解这些病毒受体相互作用对于预测和管理WEEV疫情至关重要.
这项研究提供了对 arbovirus 演化和神经侵入性 alphavirus 背后的机制的见解.

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