State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
University of the Chinese Academy of Sciences, Beijing, China.
Antimicrob Agents Chemother. 2021 May 18;65(6). doi: 10.1128/AAC.00113-21.
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 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.
虫媒乙型脑炎病毒（JEV）在全球范围内可引起严重疾病，且与高发病率和死亡率相关。为了鉴定潜在的宿主治疗靶点，我们使用重组 JEV 颗粒进行了高通量受体酪氨酸激酶小干扰 RNA 文库筛选。两轮筛选后，血小板衍生生长因子受体β（PDGFRβ）被鉴定为命中靶点。敲低 可阻断 JEV 感染，而 PDGFRβ 的转互补可部分恢复其感染性。已经被批准用于治疗恶性转移性癌症的 PDGFRβ 抑制剂伊马替尼可通过降低脑部病毒载量来保护小鼠免受 JEV 诱导的致死性，同时消除与 JEV 感染相关的组织病理学变化。这些发现表明 PDGFRβ 在病毒感染中很重要，并为开发伊马替尼作为治疗 JEV 感染的潜在干预措施提供了证据。
