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In most of the world, Dengue virus (DENV) is mainly transmitted by the mosquito  Aedes aegypti  while in Europe,  Aedes albopictus  is responsible for human DENV cases since 2010. Identifying mutations that make DENV more competent for transmission by  Ae. albopictus  will help to predict emergence of epidemic strains. Ten serial passages in vivo in  Ae. albopictus  led to select DENV-1 strains with greater infectivity for this vector in vivo and in cultured mosquito cells. These changes were mediated by multiple adaptive mutations in the virus genome, including a mutation at position 10,418 in the DENV 3′UTR within an RNA stem-loop structure involved in subgenomic flavivirus RNA production. Using reverse genetics, we showed that the 10,418 mutation alone does not confer a detectable increase in transmission efficiency in vivo. These results reveal the complex adaptive landscape of DENV transmission by mosquitoes and emphasize the role of epistasis in shaping evolutionary trajectories of DENV variants.

Experimental adaptation of dengue virus 1 to Aedes albopictus mosquitoes by in vivo selection