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Summary: Understanding the transmission routes of arboviruses is key to determining their epidemiology. Here, we tested whether West Nile viruses (WNVs) are transmitted through mosquito excreta. First, we observed a high concentration of infectious units per excreta, although viruses were short lived. Second, we showed that virion excretion starts early after oral infection and remains constant for a long period, regardless of mosquito infection level. These results highlight the infectiousness of excreta from infected mosquitoes. Third, we found that both larvae and pupae were susceptible to infection, while pupae were highly permissive. Fourth, we established the proof-of-concept that immature mosquitoes can be infected by infectious excreta, demonstrating an excreta-mediated mode of transmission. Finally, by mathematically modeling excreta-mediated transmission in the field, we demonstrated that WNV can be transmitted within mosquito populations. Our study uncovers a route of transmission for mosquito-borne arboviruses, unveiling mechanisms of viral maintenance in mosquito reservoirs.

Summary: 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. : Virology; Entomology Subject Areas: Virology, Entomology