An 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-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.
Souza-Neto
Jayme A
JA
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, 615 North Wolfe Street E4209, Baltimore, MD 21205, USA.
Sim
Shuzhen
S
Dimopoulos
George
G
D000330:Aedes / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D000818:Animals; D005075:Biological Evolution; D003716:Dengue Virus / Q000276:immunology / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D017344:Genes, Insect; D007113:Immunity, Innate / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007303:Insect Vectors / Q000235:genetics / Q000276:immunology / Q000821:virology; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D005810:Multigene Family; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D019476:Insect Proteins; D050828:Protein Inhibitors of Activated STAT; D050791:STAT Transcription Factors; D053612:Janus Kinases