Superinfection Interference between Dengue-2 and Dengue-4 Viruses in Aedes aegypti Mosquitoes

Objective: Dengue virus consists of four antigenically distinct serotypes (DENV 1-4) that are transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes. In many dengue-endemic regions, co-circulation of two or more DENV serotypes is fairly common increasing the likelihood for exposure of the two vectors to multiple serotypes. We used a model system of DENV-2 and DENV-4 to investigate how prior exposure of Aedes aegypti to one DENV serotype affects its susceptibility to another serotype. Methods: Aedes aegypti mosquitoes were sequentially infected with DENV-2 and DENV-4 and the infection and dissemination rates for each virus determined. Results: We found that prior infection of Ae. aegypti mosquitoes with DENV-4 rendered them significantly less susceptible to secondary infection with DENV-2. Although the results were not statistically significant, mosquitoes infected with DENV-2 were also less susceptible to secondary infection with DENV-4. The midgut dissemination and population dissemination rates for DENV-2 were significantly higher than those of DENV-4 when either virus was administered 7 days after administration of either a non-infectious blood meal or a blood meal containing a heterologous dengue serotype. Conclusion: These results demonstrate that superinfection interference between DENV serotypes is possible within Ae. aegypti mosquitoes, but its effect on DENV epidemiology may be dependent on the fitness of interacting serotypes.