TY - JOUR
T1 - A Role for the Insulin Receptor in the Suppression of Dengue Virus and Zika Virus in Wolbachia-Infected Mosquito Cells
AU - Haqshenas, Gholamreza
AU - Terradas, Gerard
AU - Paradkar, Prasad N.
AU - Duchemin, Jean Bernard
AU - McGraw, Elizabeth A.
AU - Doerig, Christian
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2019/1/15
Y1 - 2019/1/15
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85059825038
UR - https://www.scopus.com/pages/publications/85059825038#tab=citedBy
U2 - 10.1016/j.celrep.2018.12.068
DO - 10.1016/j.celrep.2018.12.068
M3 - Article
C2 - 30650347
AN - SCOPUS:85059825038
SN - 2211-1247
VL - 26
SP - 529-535.e3
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -