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

IF 42.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell 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

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.