Ramesh K. auteur aut IRD Walvekar V. A. auteur aut IRD Wong B. auteur aut IRD Sayed A. M. M. auteur aut IRD Missé Dorothée auteur aut IRD Kini R. M. auteur aut IRD Mok Y. K. auteur aut IRD Pompon Julien auteur aut IRD text journalArticle eng text/pdf reformatted digital access Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human fibrinolytic factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes. specialized 052 050 020 21 564-+ 2019 https://www.documentation.ird.fr/hor/fdi:010077462 10.1016/j.isci.2019.10.056 [F B010077462] https://www.documentation.ird.fr/hor/fdi:010077462 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers20-01/010077462.pdf IRD - Base Horizon / Pleins textes 2020-02-05 2025-02-24 fdi:010077462 fre