Integrin αvβ3 promotes infection by Japanese encephalitis virus

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is one of the major causes of viral encephalitis diseases worldwide. The JEV envelope protein facilitates viral entry, and its domain III contains an Arg-Gly-Asp (RGD) motif, that may modulate JEV entry through the RGD-binding integrin. In this study, the roles of integrin alpha v and beta 3 on the infection of JEV were evaluated. Reduced expression of integrin alpha v/beta 3 by special shRNA confers 2 to 4-fold inhibition of JEV replication in BHK-21 cells. Meanwhile, antibodies specific for integrin alpha v/beta 3 displayed similar to 58% and similar to 33% inhibition of JEV infectivity and RGD-specific peptides produced 36% of inhibition. Expression of E protein and JEV RNA loads were clearly increased in CHO cells transfected with cDNA encoding human integrin beta 3. Moreover, integrin av mediates JEV infection in viral binding stage of life cycle. Therefore, our study suggested that integrin av and beta 3 serve as a host factor associated with JEV entry into the target cells. (C) 2016 Elsevier Ltd. All rights reserved.