Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, VIC 3800, Australia.
School of Biological Sciences, Monash University, Clayton, VIC 3800, Australia.
Cell Rep. 2019 Jan 15;26(3):529-535.e3. doi: 10.1016/j.celrep.2018.12.068.
Wolbachia-infected mosquitoes are refractory to super-infection with arthropod-borne pathogens, but the role of host cell signaling proteins in pathogen-blocking mechanisms remains to be elucidated. Here, we use an antibody microarray approach to provide a comprehensive picture of the signaling response of Aedes aegypti-derived cells to Wolbachia. This approach identifies the host cell insulin receptor as being downregulated by the bacterium. Furthermore, siRNA-mediated knockdown and treatment with a small-molecule inhibitor of the insulin receptor kinase concur to assign a crucial role for this enzyme in the replication of dengue and Zika viruses in cultured mosquito cells. Finally, we show that the production of Zika virus in Wolbachia-free live mosquitoes is impaired by treatment with the selective inhibitor mimicking Wolbachia infection. This study identifies Wolbachia-mediated downregulation of insulin receptor kinase activity as a mechanism contributing to the blocking of super-infection by arboviruses.
感染沃尔巴克氏体的蚊子对节肢动物传播的病原体的再次感染具有抗性，但宿主细胞信号蛋白在病原体阻断机制中的作用仍有待阐明。在这里，我们使用抗体微阵列方法来提供一种全面的方式来描述埃及伊蚊细胞对沃尔巴克氏体的信号反应。这种方法确定了宿主细胞胰岛素受体被细菌下调。此外，siRNA 介导的敲低和胰岛素受体激酶的小分子抑制剂处理一致认为，该酶在培养的蚊子细胞中复制登革热和寨卡病毒中起着至关重要的作用。最后，我们表明，用模仿沃尔巴克氏体感染的选择性抑制剂处理会损害无沃尔巴克氏体的活体蚊子中寨卡病毒的产生。这项研究确定了沃尔巴克氏体介导的胰岛素受体激酶活性下调是阻止虫媒病毒再次感染的机制之一。
