| Literature DB >> 34559985 |
Safder S Ganaie1, Madeline M Schwarz2, Cynthia M McMillen2, David A Price1, Annie X Feng1, Joseph R Albe3, Wenjie Wang1, Shane Miersch4, Anthony Orvedahl5, Aidan R Cole1, Monica F Sentmanat6, Nawneet Mishra1, Devin A Boyles3, Zachary T Koenig2, Michael R Kujawa2, Matthew A Demers3, Ryan M Hoehl3, Austin B Moyle7, Nicole D Wagner7, Sarah H Stubbs8, Lia Cardarelli4, Joan Teyra4, Anita McElroy9, Michael L Gross7, Sean P J Whelan10, John Doench11, Xiaoxia Cui6, Tom J Brett12, Sachdev S Sidhu4, Herbert W Virgin13, Takeshi Egawa1, Daisy W Leung14, Gaya K Amarasinghe15, Amy L Hartman16.
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 (mRAPD3) and anti-Lrp1 antibodies neutralizes RVFV infection in taxonomically diverse cell lines. Mice treated with mRAPD3 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.Entities:
Keywords: CRISPR screen; Lrp1; Rift Valley fever virus; viral entry
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Year: 2021 PMID： 34559985 PMCID： PMC8786218 DOI： 10.1016/j.cell.2021.09.001
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850