Lrp1 is a host entry factor for Rift Valley fever virus.

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL Journal of Chemical Theory and Computation Pub Date : 2021-09-30 Epub Date: 2021-09-23 DOI:10.1016/j.cell.2021.09.001

Safder S Ganaie, Madeline M Schwarz, Cynthia M McMillen, David A Price, Annie X Feng, Joseph R Albe, Wenjie Wang, Shane Miersch, Anthony Orvedahl, Aidan R Cole, Monica F Sentmanat, Nawneet Mishra, Devin A Boyles, Zachary T Koenig, Michael R Kujawa, Matthew A Demers, Ryan M Hoehl, Austin B Moyle, Nicole D Wagner, Sarah H Stubbs, Lia Cardarelli, Joan Teyra, Anita McElroy, Michael L Gross, Sean P J Whelan, John Doench, Xiaoxia Cui, Tom J Brett, Sachdev S Sidhu, Herbert W Virgin, Takeshi Egawa, Daisy W Leung, Gaya K Amarasinghe, Amy L Hartman

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引用次数: 38

Abstract

Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFV entry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorly defined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-related protein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associated protein (RAP) as critical host factors for RVFV infection. RVFV Gn directly binds to specific Lrp1 clusters and is glycosylation independent. Exogenous addition of murine RAP domain 3 (mRAP_D3) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse cell lines. Mice treated with mRAP_D3 and infected with pathogenic RVFV are protected from disease and death. A mutant mRAPD3 that binds Lrp1 weakly failed to protect from RVFV infection. Together, these data support Lrp1 as a host entry factor for RVFV infection and define a new target to limit RVFV infections.

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Lrp1是裂谷热病毒的宿主进入因子。

裂谷热病毒(RVFV)是一种具有大流行潜力的人畜共患病原体。裂谷热病毒的进入是由病毒糖蛋白(Gn)介导的，但宿主进入因子仍然不明确。我们的全基因组CRISPR筛选鉴定出低密度脂蛋白受体相关蛋白1(小鼠Lrp1/人Lrp1)、热休克蛋白(Grp94)和受体相关蛋白(RAP)是RVFV感染的关键宿主因子。RVFV Gn直接结合特定的Lrp1簇，并且不依赖于糖基化。外源性添加小鼠RAP结构域3 (mRAPD3)和抗lrp1抗体可以在不同的细胞系中中和RVFV感染。用mRAPD3治疗并感染致病性RVFV的小鼠免受疾病和死亡的保护。与Lrp1结合较弱的mRAPD3突变体未能保护人们免受裂谷病毒感染。总之，这些数据支持Lrp1作为裂谷热病毒感染的宿主进入因子，并确定了限制裂谷热病毒感染的新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.