RNAi screening reveals requirement for PDGFRβ in JEV infection.

Abstract

Mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality. To identify potential host therapeutic targets, a high-throughput receptor tyrosine kinase small interfering RNA library screening was performed with recombinant JEV particles. Platelet-derived growth factor receptor beta (PDGFR{beta}) was identified as a hit after two rounds of screening. Knockdown of PDGFR{beta} blocked JEV infection, and trans-complementation of PDGFR{beta} could partly restore its infectivity. The PDGFR{beta} inhibitor imatinib, which has been approved for the treatment of malignant metastatic cancer, protected mice against JEV-induced lethality by decreasing the viral load in the brain, while abrogating the histopathological changes associated with JEV infection. These findings demonstrated that PDGFR{beta} is important in viral infection and provided evidence for the potential to develop imatinib as a therapeutic intervention against JEV infection.