Virus-derived DNA drives mosquito vector tolerance to arboviral infection

Bertsy Goic, Kenneth A. Stapleford, Lionel Frangeul, Aurélien J. Doucet, Valérie Gausson, Hervé Blanc, Nidia Schemmel-Jofre, Gael Cristofari, Louis Lambrechts, Marco Vignuzzi and Maria-Carla Saleh ()
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Bertsy Goic: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569
Kenneth A. Stapleford: Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569
Lionel Frangeul: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569
Aurélien J. Doucet: IRCAN, INSERM U1081, Centre National de la Recherche Scientifique UMR 7284, University of Nice—Sophia-Antipolis
Valérie Gausson: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569
Hervé Blanc: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569
Nidia Schemmel-Jofre: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569
Gael Cristofari: IRCAN, INSERM U1081, Centre National de la Recherche Scientifique UMR 7284, University of Nice—Sophia-Antipolis
Louis Lambrechts: Institut Pasteur, Insect-Virus Interactions Group, Centre National de la Recherche Scientifique URA 3012
Marco Vignuzzi: Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569
Maria-Carla Saleh: Institut Pasteur, Viruses and RNA Interference Unit, Centre National de la Recherche Scientifique UMR 3569

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12410

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