Neuropilin 1 is an entry receptor for KSHV infection of mesenchymal stem cell through TGFBR1/2-mediated macropinocytosis.
Sci Adv
; 9(21): eadg1778, 2023 05 24.
Article
em En
| MEDLINE
| ID: mdl-37224259
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-ß receptor type 2 (TGFBR2) through their respective cytoplasmic domains and thus activates the TGFBR1/2 complex, which facilitates the macropinocytosis-mediated KSHV internalization via the small GTPases Cdc42 and Rac1. Together, these findings implicate that KSHV has evolved a strategy to invade MSCs by harnessing NRP1 and TGF-beta receptors to stimulate macropinocytosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Herpesvirus Humano 8
/
Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article