Superior infectivity for mosquito vectors contributes to competitive displacement among strains of dengue virus

To be transmitted by a mosquito, DENV must infect and replicate in the midgut, disseminate into the hemocoel, infect the salivary glands, and be released into the saliva. The ability of the native and invasive DENV3 strains to complete the first three steps of this process in Aedes aegypti mosquitoes was measured in vivo. The invasive strain infected a similar proportion of mosquitoes as the native strain but replicated to significantly higher titers in the midgut and disseminated with significantly greater efficiency than the native strain. In contrast, the native and invasive strain showed no significant difference in replication in cultured mosquito, monkey or human cells.The invasive DENV3 strain infects and disseminates in Ae. aegypti more efficiently than the displaced native DENV3 strain, suggesting that the invasive strain is transmitted more efficiently. Replication in cultured cells did not adequately characterize the known phenotypic differences between native and invasive DENV3 strains. Infection dynamics within the vector may have a significant impact on the spread and replacement of dengue virus lineages.The mechanisms that drive competitive displacement of one species by another have received considerable attention from ecologists in the context of species invasions by free-living organisms [1-7]. Competitive displacement may play an equally important role in the dynamics of emerging infectious diseases. One of several mechanisms of disease emergence [8] is the displacement of a pathogen strain of low virulence (defined here as the impact of the pathogen on host fitness [9]), by a new, more virulent strain. The mechanisms that facilitate competitive displacement of pathogens are broadly similar to those that act in free-living organisms [7]: (i) exploitation competition, in which the pathogen with the highest rate of transmission pre-empts access to hosts either by killing them [10] or by generating cross-immunity that prevents infection by competitor