title: Engineered Aedes aegypti JAK/STAT Pathway-Mediated Immunity to Dengue Virus.
abstract: We have developed genetically modified Ae. aegypti mosquitoes that activate the conserved antiviral JAK/STAT pathway in the fat body tissue, by overexpressing either the receptor Dome or the Janus kinase Hop by the blood feeding-induced vitellogenin (Vg) promoter. Transgene expression inhibits infection with several dengue virus (DENV) serotypes in the midgut as well as systemically and in the salivary glands. The impact of the transgenes Dome and Hop on mosquito longevity was minimal, but it resulted in a compromised fecundity when compared to wild-type mosquitoes. Overexpression of Dome and Hop resulted in profound transcriptome regulation in the fat body tissue as well as the midgut tissue, pinpointing several expression signatures that reflect mechanisms of DENV restriction. Our transcriptome studies and reverse genetic analyses suggested that enrichment of DENV restriction factor and depletion of DENV host factor transcripts likely accounts for the DENV inhibition, and they allowed us to identify novel factors that modulate infection. Interestingly, the fat body-specific activation of the JAK/STAT pathway did not result in any enhanced resistance to Zika virus (ZIKV) or chikungunya virus (CHIKV) infection, thereby indicating a possible specialization of the pathway's antiviral role.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Natapong
authors.initials: N
authors.lastname: Jupatanakul
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sim
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Yesseinia I
authors.initials: YI
authors.lastname: Angleró-Rodríguez
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Jayme
authors.initials: J
authors.lastname: Souza-Neto
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Das
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Poti
authors.affiliation: Department of Pathology and Center of Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston TX, United States of America.
authors.forename: Shannan L
authors.initials: SL
authors.lastname: Rossi
authors.affiliation: Department of Pathology and Center of Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston TX, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bergren
authors.affiliation: Department of Pathology and Center of Biodefense and Emerging Infectious Diseases, Center for Tropical Diseases, Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston TX, United States of America.
authors.forename: Nikos
authors.initials: N
authors.lastname: Vasilakis
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: George
authors.identifier: 0000-0001-6755-8111
authors.initials: G
authors.lastname: Dimopoulos
mesh_terms: D000330:Aedes / Q000235:genetics* / Q000276:immunology / Q000821:virology; D000818:Animals; D003715:Dengue / Q000635:transmission* / Q000821:virology; D003716:Dengue Virus / Q000502:physiology*; D005216:Fat Body / Q000276:immunology; D005818:Genetic Engineering; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000276:immunology*; D007303:Insect Vectors / Q000235:genetics* / Q000276:immunology / Q000821:virology; D053612:Janus Kinases / Q000235:genetics / Q000276:immunology*; D051379:Mice; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D019476:Insect Proteins; D050791:STAT Transcription Factors; D053612:Janus Kinases