Rna Interference Screening Reveals Requirement For Platelet-Derived Growth Factor Receptor Beta In Japanese Encephalitis Virus Infection

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 transcomplementation 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.