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RNAi screening reveals requirement for PDGFRβ in JEV infection.

By Minmin Zhou, Shaobo Wang, Jiao Guo, Yang Liu, Junyuan Cao, Xiaohao Lan, Xiaoying Jia, Bo Zhang, Gengfu Xiao, Wei Wang

Posted 22 Jan 2021
bioRxiv DOI: 10.1101/2021.01.21.427722

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.

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