Integrin ?v?5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy.

ABSTRACT: We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin ?v?5 as an internalization factor for Zika virus (ZIKV). Expression of ?v?5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin ?v?5, but not ?v?3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin ?v?5-blocking antibody. ?v?5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, ?v?5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin ?v?5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections.

SUBMITTER: Wang S 

PROVIDER: S-EPMC7293422 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature