Neuropilin 1 is an entry receptor for KSHV infection of mesenchymal stem cell through TGFBR1/2-mediated macropinocytosis.

ABSTRACT: Kaposi's sarcoma-associated herpesvirus (KSHV) has been implicated in the pathogenesis of Kaposi's sarcoma (KS) and other malignancies. The cellular origin of KS has been suggested to be either mesenchymal stem cells (MSCs) or endothelial cells. However, receptor(s) for KSHV to infect MSCs remains unknown. By combining bioinformatics analysis and shRNA screening, we identify neuropilin 1 (NRP1) as an entry receptor for KSHV infection of MSCs. Functionally, NRP1 knockout and overexpression in MSCs significantly reduce and promote, respectively, KSHV infection. Mechanistically, NRP1 facilitated the binding and internalization of KSHV by interacting with KSHV glycoprotein B (gB), which was blocked by soluble NRP1 protein. Furthermore, NRP1 interacts with TGF-β receptor type 2 (TGFBR2) through

SUBMITTER: Lu ZZ 

PROVIDER: S-EPMC10208568 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature