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Lrp1是裂谷热病毒的宿主进入因子
作者:小柯机器人 发布时间:2021/9/25 22:06:25

美国匹兹堡大学Amy L. Hartman、圣路易斯华盛顿大学Gaya K. Amarasinghe等研究人员合作发现,Lrp1是裂谷热病毒的宿主进入因子。2021年9月23日,《细胞》杂志在线发表了这项成果。

研究人员通过全基因组CRISPR筛选确定了低密度脂蛋白受体相关蛋白1(小鼠Lrp1/人类LRP1)、热休克蛋白(Grp94)和受体相关蛋白(RAP)为裂谷热病毒(RVFV)感染的关键宿主因子。RVFV病毒糖蛋白(Gn)直接与特定的Lrp1簇结合,并且与糖基化无关。外源性添加小鼠RAP结构域3(mRAPD3)和抗Lrp1抗体可中和RVFV在分类学上不同细胞系的感染。用mRAPD3处理的小鼠在感染了致病性RVFV后可以避免发病和死亡。一个与Lrp1结合较弱的突变体mRAPD3不能保护RVFV感染。总之,这些数据支持Lrp1作为RVFV感染的宿主进入因子,并确定了限制RVFV感染的新靶标。

据了解,RVFV是一种具有大流行潜力的人畜共患病原体。RVFV的进入是由Gn介导的,但宿主的进入因素仍然定义不清。

附:英文原文

Title: Lrp1 is a host entry factor for Rift Valley fever virus

Author: 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

Issue&Volume: 2021-09-23

Abstract: Rift Valley fever virus (RVFV) is a zoonotic pathogen with pandemic potential. RVFVentry is mediated by the viral glycoprotein (Gn), but host entry factors remain poorlydefined. Our genome-wide CRISPR screen identified low-density lipoprotein receptor-relatedprotein 1 (mouse Lrp1/human LRP1), heat shock protein (Grp94), and receptor-associatedprotein (RAP) as critical host factors for RVFV infection. RVFV Gn directly bindsto specific Lrp1 clusters and is glycosylation independent. Exogenous addition ofmurine RAP domain 3 (mRAPD3) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse celllines. Mice treated with mRAPD3 and infected with pathogenic RVFV are protected from disease and death. A mutantmRAPD3 that binds Lrp1 weakly failed to protect from RVFV infection. Together, thesedata support Lrp1 as a host entry factor for RVFV infection and define a new targetto limit RVFV infections.

DOI: 10.1016/j.cell.2021.09.001

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01048-5

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/