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Cell Rep. 2019 Nov 12;29(7):1946-1960.e5. doi: 10.1016/j.celrep.2019.10.029.

Insulin Potentiates JAK/STAT Signaling to Broadly Inhibit Flavivirus Replication in Insect Vectors.

Author information

1
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
2
Department of Entomology, Plant Pathology, and Nematology, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID 83844, USA.
3
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
4
Department of Entomology, Plant Pathology, and Nematology, College of Agricultural and Life Sciences, University of Idaho, Moscow, ID 83844, USA; Department of Biological Sciences, College of Science, University of Idaho, Moscow, ID 83844, USA.
5
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA; Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. Electronic address: alan.goodman@wsu.edu.

Abstract

The World Health Organization estimates that more than half of the world's population is at risk for vector-borne diseases, including arboviruses. Because many arboviruses are mosquito borne, investigation of the insect immune response will help identify targets to reduce the spread of arboviruses. Here, we use a genetic screening approach to identify an insulin-like receptor as a component of the immune response to arboviral infection. We determine that vertebrate insulin reduces West Nile virus (WNV) replication in Drosophila melanogaster as well as WNV, Zika, and dengue virus titers in mosquito cells. Mechanistically, we show that insulin signaling activates the JAK/STAT, but not RNAi, pathway via ERK to control infection in Drosophila cells and Culex mosquitoes through an integrated immune response. Finally, we validate that insulin priming of adult female Culex mosquitoes through a blood meal reduces WNV infection, demonstrating an essential role for insulin signaling in insect antiviral responses to human pathogens.

KEYWORDS:

Culex quinquefasciatus; DGRP; Drosophila melanogaster; ERK; Kunjin virus; West Nile virus; Zika virus; dengue virus; innate immunity; mosquito

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