Dengue virus harnesses mosquito Syntenin to load and secrete viral RNA into salivary exosomes
Abstract
Viruses exploit extracellular vesicles (EVs) to transfer infection-enhancing viral RNAs. However, mechanisms underlying viral RNA loading remain elusive. We leveraged our previous discovery that dengue virus secretes transmission-enhancing subgenomic flaviviral RNA (sfRNA) into mosquito salivary EVs to investigate viral RNA loading mechanism. We demonstrate that sfRNA alone promotes the secretion of sfRNA-containing EVs marked by the mosquito EV biogenesis protein AeSyntenin, by applying microscopy and viral genetic editing in in vitro and in vivo models. SfRNA via its stem loop structures interacts intracellularly with mosquito AeSyntenin and this interaction is selectively maintained within EVs as shown by complementary RNA-affinity chromatography and RNA immunoprecipitation, and AI-based prediction. Finally, we used systemic and salivary gland-specific protein depletion to establish a functional role for mosquito AeSyntenin in exosome production and salivary secretion of sfRNA. We propose that sfRNA binds AeSyntenin to drive its selective packaging and release into exosomes, elucidating a mechanism for viral RNA incorporation into EVs.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (23)
Florian Rachenne
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Norman Schneider
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Félix Rey-Cadilhac
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Idalba Serrato-Pomar
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Lauryne Pruvost
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Laura Di Pietro
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Jacques Dainat
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Audrey Vernet
Plant Health Institute of Montpellier, University of Montpellier, Institut of Research for development
Chantal Cazevieille
Université Montpellier, INSERM U1298, Institute for Neurosciences of Montpellier
Aurélie Ancelin
Centre de Biologie Structurale, Electronic Microscopy Platform, CNRS
Joséphine Lai Kee Him
Centre de Biologie Structurale, Electronic Microscopy Platform, CNRS
Sander Jansen
Katholic University Leuven, Department of Microbiology, Immunology and Transplantion, Rega Institute, Laboratory of Molecular Vaccinology and Vaccine Discovery
Elliott F. Miot
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Jérémy Fraering
Plateforme Protéomique Strasbourg-Esplanade, CNRS UAR1589, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg
Laurianne Simon
Institut Charles Gerhardt Montpellier, University of Montpellier, CNRS, Ecole Nationale Supérieure de Chimie de Montpellier
Dorothée Missé
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS
Marie Morille
Institut Charles Gerhardt Montpellier, University of Montpellier, CNRS, Ecole Nationale Supérieure de Chimie de Montpellier
Philippe Hammann
Plateforme Protéomique Strasbourg-Esplanade, CNRS UAR1589, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg
Martial Seveno
BioCampus Montpellier, University of Montpellier, CNRS, INSERM
Serge Urbach
Institut de Génétique Fontionnel, University of Montpellier, CNRS, INSERM
Kai Dallmeier
Katholic University Leuven, Department of Microbiology, Immunology and Transplantion, Rega Institute, Laboratory of Molecular Vaccinology and Vaccine Discovery
Éric Marois
Institute of Molecular and Cellular Biology, University of Strasbourg, CNRS, Inserm
Julien Pompon
Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Controle, University of Montpellier, Institut of Research for development, CNRS