Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18.

Human FcRn Is a Two-in-One Attachment-Uncoating Receptor for Echovirus 18.
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人FcRN是ECHO病毒18的二合一附着去涂层受体。

DOI:
10.1128/mbio.01166-22
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发表时间:
2022-08-30
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学1区
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病毒-受体相互作用决定病毒的宿主范围和组织嗜性。在我们之前的研究中发现,CD 55和人新生儿Fc受体(FcRn)是一些与埃可病毒相关的肠道病毒B血清型的结合和未包被受体。埃可病毒18(Echovirus 18,E18)是肠道病毒B型的一种,是小儿无菌性脑膜炎和病毒性脑炎的重要病原。然而,它不使用CD 55作为关键宿主因子。我们进行了CRISPR/Cas9敲除筛选,以确定受体和进入机制,并确定FcRn作为E18的双功能受体。敲除编码FcRn的两个亚基的FCGRT和B2 M,防止了E18和相同生理簇中的其他埃可病毒的感染。然后,我们阐明了E18受体识别的分子机制,使用低温电子显微镜。FCGRT亚基与峡谷区的结合使口袋周围的残基旋转,触发口袋因子的释放,如在其他肠道病毒种B成员中观察到的。
Virus-receptor interactions determine viral host range and tissue tropism. CD55 and human neonatal Fc receptor (FcRn) were found to be the binding and uncoating receptors for some of the echovirus-related enterovirus species B serotypes in our previous study. Echovirus 18 (E18), as a member of enterovirus species B, is a significant causative agent of aseptic meningitis and viral encephalitis in children. However, it does not use CD55 as a critical host factor. We conducted CRISPR/Cas9 knockout screening to determine the receptors and entry mechanisms and identified FcRn working as a dual-function receptor for E18. Knockout of FCGRT and B2M, which encode the two subunits of FcRn, prevented infection by E18 and other echoviruses in the same physiological cluster. We then elucidated the underlying molecular mechanism of receptor recognition by E18 using cryogenic electron microscopy. The binding of the FCGRT subunit to the canyon region rotates the residues around the pocket, triggering the release of the pocket factor as observed for other enterovirus species B members.
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