evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense

Here, we show that the major mosquito vector for dengue virus uses the JAK-STAT pathway to control virus infection. Dengue virus infection in Aedes aegypti mosquitoes activates the JAK-STAT immune signaling pathway. The mosquito's susceptibility to dengue virus infection increases when the JAK-...

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Published in:	Proceedings of the National Academy of Sciences - PNAS 2009-10, Vol.106 (42), p.17841-17846
Main Authors:	Souza-Neto, Jayme A, Sim, Shuzhen, Dimopoulos, George
Format:	Article
Language:	eng
Subjects:	Aedes - genetics Aedes - immunology Aedes - virology Aedes aegypti Animals Binding sites Biological Evolution Biological Sciences Dengue Dengue fever Dengue virus Dengue Virus - immunology Dengue Virus - pathogenicity Drosophila Gene Expression Profiling Gene expression regulation Genes Genes, Insect Immunity, Innate - genetics Infections Insect Proteins - genetics Insect Proteins - metabolism Insect Vectors - genetics Insect Vectors - immunology Insect Vectors - virology Janus Kinases - genetics Janus Kinases - metabolism Midgut Models, Biological Mosquitoes Mosquitos Multigene Family Protein Inhibitors of Activated STAT - genetics Protein Inhibitors of Activated STAT - metabolism RNA Interference Signal Transduction STAT Transcription Factors - genetics STAT Transcription Factors - metabolism Tolls Viruses
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Summary:	Here, we show that the major mosquito vector for dengue virus uses the JAK-STAT pathway to control virus infection. Dengue virus infection in Aedes aegypti mosquitoes activates the JAK-STAT immune signaling pathway. The mosquito's susceptibility to dengue virus infection increases when the JAK-STAT pathway is suppressed through RNAi depletion of its receptor Domeless (Dome) and the Janus kinase (Hop), whereas mosquitoes become more resistant to the virus when the negative regulator of the JAK-STAT pathway, PIAS, is silenced. The JAK-STAT pathway exerts its anti-dengue activity presumably through one or several STAT-regulated effectors. We have identified, and partially characterized, two JAK-STAT pathway-regulated and infection-responsive dengue virus restriction factors (DVRFs) that contain putative STAT-binding sites in their promoter regions. Our data suggest that the JAK-STAT pathway is part of the A. aegypti mosquito's anti-dengue defense and may act independently of the Toll pathway and the RNAi-mediated antiviral defenses.
ISSN:	0027-8424 1091-6490