Dengue virus harnesses mosquito Syntenin to load and secrete viral RNA into salivary exosomes Rachenne F. auteur aut IRD Schneider Norman auteur aut IRD Rey-Cadilhac F. auteur aut IRD Serrato-Pomar I. auteur aut IRD Pruvost Lauryne auteur aut IRD Di Pietro L. auteur aut IRD Dainat Jacques auteur aut IRD Vernet Audrey auteur aut IRD Cazevieille C. auteur aut IRD Ancelin A. auteur aut IRD Him J. L. K. auteur aut IRD Jansen S. auteur aut IRD Miot E. F. auteur aut IRD Fraering Jeremy auteur aut IRD Simon L. auteur aut IRD Missé Dorothée auteur aut IRD Morille M. auteur aut IRD Hammann P. auteur aut IRD Seveno M. auteur aut IRD Urbach S. auteur aut IRD Dallmeier K. auteur aut IRD Marois É auteur aut IRD Pompon Julien auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized viral dissemination exosomes |orthoflavivirus mosquito-borne diseases 052 020 Proceedings of the National Academy of Sciences of the United States of America 123 12 e2520697123 [12 p.] 2026 0027-8424 https://www.documentation.ird.fr/hor/fdi:010096916 10.1073/pnas.2520697123 0027-8424 [F B010096916] https://www.documentation.ird.fr/hor/fdi:010096916 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2026-05/010096916.pdf IRD - Base Horizon / Pleins textes 2026-05-20 2026-05-20 fdi:010096916 fre