Lrp1 is a host entry factor for Rift Valley fever virus (RVFV)

Lrp1 is a member of the low-density lipoprotein (LDL) receptor family, and they play roles in lipid metabolism and in several endocytic and inflammatory signalling pathways. Screening of genome-wide CRISPR/Cas9 libraries revealed that Lrp1, together with its modulators, RAP and GRP94, are essential host factors for the virulence of RVFV. Lrp1 is conserved across species and different cell types, which could explain the wide host range of the zoonotic virus. Knockout of Lrp1, RAP and GRP94 significantly reduced infection by both the pathogenic and attenuated strains of RVFV. Reduced infection was observed in both cell lines and in primary mouse embryonic fibroblasts. The direct interaction between Lrp1 and glycoprotein was analyzed and found to play an important role in the infection process. Targeting Lrp1 offers a promising therapeutic target against RVFV, which has a pandemic potential.
(MRM)