LDLRAD3 is a receptor for Venezuelan equine encephalitis virus.
LDLRAD3 is a receptor for Venezuelan equine encephalitis virus.
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DOI：
10.1038/s41586-020-2915-3
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发表时间：
2020-12
期刊：
影响因子：
64.8
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Ma H;Kim AS;Kafai NM;Earnest JT;Shah AP;Case JB;Basore K;Gilliland TC;Sun C;Nelson CA;Thackray LB;Klimstra WB;Fremont DH;Diamond MS
委内瑞拉马脑炎病毒（VEEV）是一种蚊子传播的嗜神经甲病毒，可导致人类脑炎和死亡。VEEV是一个生物防御问题，因为它有可能造成气溶胶传播，而且缺乏足够的对策。VEEV进入和感染所需的宿主因素仍然缺乏特征。使用基于CRISPR/Cas9的全基因组筛选，我们鉴定了清道夫受体超家族的高度保守成员Ldlrad 3作为VEEV的受体。小鼠Ldlrad 3或人LDLRAD 3的基因编辑导致神经元细胞的病毒感染显著减少，其在互补后恢复。Ldlrad 3直接与VEEV颗粒结合并增强病毒附着和内化到细胞中。遗传研究表明，Ldlrad 3的结构域1（D1）对于支持VEEV感染是必需的且足够的，并且抗Ldlrad 3抗体和Ldlrad 3-D1-Fc融合蛋白在细胞培养物中阻断VEEV感染。值得注意的是，在Ldlrad 3缺失的小鼠中消除了VEEV发病机制，并且施用Ldlrad 3-D1-Fc消除了由多种VEEV亚型（包括高毒力毒株）引起的疾病。诱饵受体融合蛋白的开发创造了预防人类严重VEEV感染和疾病的策略。
Venezuelan equine encephalitis virus (VEEV) is a mosquito-transmitted neurotropic alphavirus that causes encephalitis and death in humans. VEEV is a biodefense concern because of its potential for aerosol spread and lack of sufficient countermeasures. The host factors required for VEEV entry and infection remain poorly characterized. Using a genome-wide CRISPR/Cas9-based screen, we identify Ldlrad3, a highly conserved member of the scavenger receptor superfamily, as a receptor for VEEV. Gene editing of mouse Ldlrad3 or human LDLRAD3 results in markedly reduced viral infection of neuronal cells, which is restored upon complementation. Ldlrad3 binds directly to VEEV particles and enhances virus attachment and internalization into cells. Genetic studies indicate that domain 1 (D1) of Ldlrad3 is necessary and sufficient to support VEEV infection, and both anti-Ldlrad3 antibodies and a Ldlrad3-D1-Fc fusion protein block VEEV infection in cell culture. Remarkably, VEEV pathogenesis is abrogated in mice with deletions in Ldlrad3, and administration of Ldlrad3-D1-Fc abolishes disease caused by multiple VEEV subtypes including highly virulent strains. The development of a decoy receptor fusion protein creates a strategy for preventing severe VEEV infection and disease in humans.
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影响因子：
6.7
作者：
Pal, Pankaj;Dowd, Kimberly A.;Diamond, Michael S.
通讯作者：
Diamond, Michael S.
影响因子：
64.5
作者：
Basore, Katherine;Kim, Arthur S.;Fremont, Daved H.
通讯作者：
Fremont, Daved H.
DOI：
10.1523/jneurosci.5065-10.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ranganathan S;Noyes NC;Migliorini M;Winkles JA;Battey FD;Hyman BT;Smith E;Yepes M;Mikhailenko I;Strickland DK
通讯作者：
Strickland DK
影响因子：
5.4
作者：
KINNEY, RM;CHANG, GJ;TRENT, DW
通讯作者：
TRENT, DW
影响因子：
5.4
作者：
Lubman, Olga Y.;Cella, Marina;Fremont, Daved H.
通讯作者：
Fremont, Daved H.