A Role for the Insulin Receptor in the Suppression of Dengue Virus and Zika Virus in Wolbachia-Infected Mosquito Cells

Gholamreza Haqshenas (1) , Gerard Terradas (1) , Prasad N. Paradkar (2) , Jean-Bernard Duchemin (2) , Elizabeth A. Mcgraw (1, 3) , Christian Doerig (1)

1 Monash University [Clayton]
2 AAHL - Australian Animal Health Laboratory
3 Penn State - Pennsylvania State University

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.

Mots clés: Aedes aegypti; Dengue virus; Wolbachia; Zika virus; antibody microarray; cell signaling; insulin receptor; insulin receptor kinase inhibitor; mosquito; siRNA

Domaines: Parasitologie; Virologie; Santé; Zoologie des invertébrés

Gholamreza Haqshenas, Gerard Terradas, Prasad N. Paradkar, Jean-Bernard Duchemin, Elizabeth A. Mcgraw, et al.. A Role for the Insulin Receptor in the Suppression of Dengue Virus and Zika Virus in Wolbachia-Infected Mosquito Cells. Cell Reports, 2019, 26 (3), pp.529-535.e3. ⟨10.1016/j.celrep.2018.12.068⟩. ⟨hal-03235203⟩