SNX17 facilitates entry and infection of Rift Valley fever virus and related bunyaviruses

Bunyaviruses are a group of multisegmented, negative-sense RNA viruses. Rift Valley fever virus (RVFV) is a representative member that can cause sporadic human outbreaks. We previously identified low-density lipoprotein receptor-related protein 1 (LRP1) as a host entry factor for RVFV and several bunyaviruses. This screen also identified additional factors as proviral host proteins, including sorting nexin 17 (SNX17). Here, we describe efforts to characterize SNX17 in bunyaviral infection. Our findings reveal that the removal of SNX17 results in a substantial reduction of RVFV infection in SNX17 knockout (KO) cells. Further analysis revealed that SNX17 removal resulted in a reduction but not complete elimination of LRP1 expression. Importantly, SNX17 interacts with full-length RVFV Gc and, upon infection by RVFV, co-migrates with RVFV to late endosomes. In addition to RVFV, several other bunyaviruses also appear to be dependent on SNX17 for infection, suggesting a potential broader role for SNX17 in bunyaviral entry.