Density-dependent competitive suppression of sylvatic dengue virus by endemic dengue virus in cultured mosquito cells

Mosquito-borne dengue viruses are maintained in two discrete transmission cycles: a sylvatic cycle between nonhuman primates and sylvatic Aedes mosquitoes, and an endemic cycle between humans and peridomestic Aedes (primarily Ae. aegypti and Ae. albopictus). Most sylvatic strains are genetically distinct from endemic strains, and human infections with sylvatic strains have been detected only rarely. Interestingly, sylvatic strains replicate as well as endemic strains in Ae. aegypti and experimental models of replication in humans, suggesting that adaptive constraints may not explain the limited spillover of sylvatic strains into the endemic cycle. Within-host competition is another mechanism known to decrease emergence of strains into occupied niches. In the current study, we examined the magnitude of competitive suppression between sylvatic and endemic dengue strains of different serotypes in pair-wise mixed infections of cultured Ae. albopictus cells to test whether the ecotype or the initial ratio of the two strains influenced the outcome of competition. Strains isolated from nonhuman primates were competitively inferior to those isolated from humans. Moreover, competition was density-dependent; the magnitude of suppression increased as the starting density of a strain relative to its competitor decreased. These data suggest that competitive inferiority in endemic vectors coupled with a numerical disadvantage relative to resident endemic strains could restrict reemergence of sylvatic strains into the endemic cycle and contribute to the ecologically correlated genetic divergence between sylvatic and endemic strains.