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 (PDGFRβ) was identified as a hit after two rounds of screening. Knockdown of PDGFRβ blocked JEV infection and transcomplementation of PDGFRβ could partly restore its infectivity. The PDGFRβ 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 PDGFRβ is important in viral infection and provided evidence for the potential to develop imatinib as a therapeutic intervention against JEV infection.
Highlights
Mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality
Using an receptor tyrosine kinases (RTKs) RNA interference (RNAi) screen library, we identified that platelet-derived growth factor receptor beta (PDGFRb) acted as a proviral gene in JEV infection
Arrays of four independent small interfering RNAs targeting 56 RTK genes grouped in a 2 by 2 mix format were transfected into human cervix epithelial (HeLa) cells
Summary
Mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality. The PDGFRb 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 PDGFRb is important in viral infection and provided evidence for the potential to develop imatinib as a therapeutic intervention against JEV infection. Using an RTK RNA interference (RNAi) screen library, we identified that platelet-derived growth factor receptor beta (PDGFRb) acted as a proviral gene in JEV infection. Imatinib, a specific PDGFRb inhibitor, could robustly inhibit JEV infection both in vitro and in vivo These results contribute to our understanding of the biology of virus entry and potentially provide new host targets for therapeutic intervention
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