| First Author | Ganaie SS | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 20 | Pages | 5163-5178.e24 |
| PubMed ID | 34559985 | Mgi Jnum | J:311489 |
| Mgi Id | MGI:6765223 | Doi | 10.1016/j.cell.2021.09.001 |
| Citation | Ganaie SS, et al. (2021) Lrp1 is a host entry factor for Rift Valley fever virus. Cell 184(20):5163-5178.e24 |
| abstractText | 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. |
