Rift Valley fever virus infects trophoblast cell lines in an LRP1-dependent manner

Abstract

Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that poses a growing global threat, causing severe disease in humans and livestock, including hepatitis, haemorrhage and encephalitis. Documented cases of vertical transmission in humans and livestock highlight risks during pregnancy. Although RVFV can directly infect the placenta, how it enters trophoblast cells remains unclear. Here, we investigated the role of low-density lipoprotein receptor-related protein 1 (LRP1), a known RVFV entry factor, in human trophoblast infection. Using JEG-3, JAR and HTR-8/SVneo trophoblast cell lines, we demonstrate that RVFV replicates to high titres and LRP1 expression varies across cell types. Competitive inhibition assays using the high-affinity LRP1 ligand murine RAP domain 3 and recombinant LRP1 fragments (cluster proteins) indicate that RVFV requires LRP1 for efficient trophoblast infection. Together, these findings implicate LRP1 as a determinant of RVFV infection at the maternal-fetal interface.