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在蜱虫中发现的克里米亚-刚果出血热病毒的一个单一突变会削弱其在人类细胞中的感染力。

A single mutation in Crimean-Congo hemorrhagic fever virus discovered in ticks impairs infectivity in human cells.

机构信息

Centers for Disease Control and Prevention, Atlanta, United States.

Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Free University Berlin, Humboldt-University Berlin, and Berlin Institute of Health, Berlin, Germany.

出版信息

Elife. 2020 Oct 21;9:e50999. doi: 10.7554/eLife.50999.

DOI:10.7554/eLife.50999
PMID:33084573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7652417/
Abstract

Crimean-Congo hemorrhagic fever (CCHF) is the most widely distributed tick-borne viral infection in the world. Strikingly, reported mortality rates for CCHF are extremely variable, ranging from 5% to 80% (Whitehouse, 2004). CCHF virus (CCHFV, ) exhibits extensive genomic sequence diversity across strains (Deyde et al., 2006; Sherifi et al., 2014). It is currently unknown if genomic diversity is a factor contributing to variation in its pathogenicity. We obtained complete genome sequences of CCHFV directly from the tick reservoir. These new strains belong to a solitary lineage named Europe 2 that is circumstantially reputed to be less pathogenic than the epidemic strains from Europe 1 lineage. We identified a single tick-specific amino acid variant in the viral glycoprotein region that dramatically reduces its fusion activity in human cells, providing evidence that a glycoprotein precursor variant, present in ticks, has severely impaired function in human cells.

摘要

克里米亚-刚果出血热(CCHF)是世界上分布最广泛的蜱传病毒性感染。引人注目的是,CCHF 的报告死亡率差异极大,范围从 5%到 80%(Whitehouse,2004)。CCHF 病毒(CCHFV,)在不同菌株之间表现出广泛的基因组序列多样性(Deyde 等人,2006;Sherifi 等人,2014)。目前尚不清楚基因组多样性是否是导致其致病性变异的因素。我们直接从蜱虫库中获得了 CCHFV 的完整基因组序列。这些新菌株属于一个名为欧洲 2 的孤立谱系,据称其致病性比来自欧洲 1 谱系的流行菌株要低。我们在病毒糖蛋白区域发现了一个单一的蜱特异性氨基酸变异,该变异极大地降低了其在人类细胞中的融合活性,这表明存在于蜱虫中的糖蛋白前体变异在人类细胞中严重功能受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b2d/7652417/257631d44663/elife-50999-resp-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b2d/7652417/2ed1e5e08af3/elife-50999-fig2.jpg
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