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

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

Cell (2021-09-25)

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

PMID34559985

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.

MATERIALS

Product Number

Brand

Product Description

362330

Sigma-Aldrich

GAG Antagonist, Surfen, The GAG Antagonist, Surfen controls the biological activity of GAG. This small molecule/inhibitor is primarily used for Activators/Inducers applications.