title: Virus-derived DNA drives mosquito vector tolerance to arboviral infection.
abstract: Mosquitoes develop long-lasting viral infections without substantial deleterious effects, despite high viral loads. This makes mosquitoes efficient vectors for emerging viral diseases with enormous burden on public health. How mosquitoes resist and/or tolerate these viruses is poorly understood. Here we show that two species of Aedes mosquitoes infected with two arboviruses from distinct families (dengue or chikungunya) generate a viral-derived DNA (vDNA) that is essential for mosquito survival and viral tolerance. Inhibition of vDNA formation leads to extreme susceptibility to viral infections, reduction of viral small RNAs due to an impaired immune response, and loss of viral tolerance. Our results highlight an essential role of vDNA in viral tolerance that allows mosquito survival and thus may be important for arbovirus dissemination and transmission. Elucidating the mechanisms of mosquito tolerance to arbovirus infection paves the way to conceptualize new antivectorial strategies to selectively eliminate arbovirus-infected mosquitoes.
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Bertsy
authors: B
authors: Goic
authors: Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Kenneth A
authors: KA
authors: Stapleford
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Lionel
authors: L
authors: Frangeul
authors: IRCAN, INSERM U1081, Centre National de la Recherche Scientifique UMR 7284, University of Nice-Sophia-Antipolis, 06107 Nice Cedex 2, France.
authors: Aurélien J
authors: AJ
authors: Doucet
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Valérie
authors: V
authors: Gausson
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.|Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Hervé
authors: H
authors: Blanc
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Nidia
authors: N
authors: Schemmel-Jofre
authors: IRCAN, INSERM U1081, Centre National de la Recherche Scientifique UMR 7284, University of Nice-Sophia-Antipolis, 06107 Nice Cedex 2, France.|FHU OncoAge, University of Nice-Sophia Antipolis, 06107 Nice, France.
authors: Gael
authors: G
authors: Cristofari
authors: Institut Pasteur, Insect-Virus Interactions Group, Centre National de la Recherche Scientifique URA 3012, 75724 Paris cedex 15, France.
authors: Louis
authors: L
authors: Lambrechts
authors: Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Marco
authors: M
authors: Vignuzzi
authors: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569, 75724 Paris cedex 15, France.
authors: Maria-Carla
authors: MC
authors: Saleh
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D001103:Arboviruses / Q000235:genetics*; D002460:Cell Line; D065632:Chikungunya Fever / Q000635:transmission / Q000821:virology; D002646:Chikungunya virus / Q000235:genetics* / Q000254:growth & development; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics*; D003715:Dengue / Q000635:transmission / Q000821:virology; D003716:Dengue Virus / Q000235:genetics* / Q000254:growth & development; D000072138:Mosquito Vectors / Q000821:virology*; D034622:RNA Interference; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D014709:Vero Cells; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral