@entity779 viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, @entity779 @entity1 ' sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during @entity281 . In particular, two residues in the @entity10242 protein coding sequence appear to be specifically acquired during @entity281 in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the @entity984 protein coding sequence that is refractory to mutation during @entity1 and mosquito @entity281 . Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses.

Analysis of Dengue Virus Genetic Diversity during XXXX and Mosquito Infection Reveals Genetic Constraints.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity984 :: ('3845', 'Gene') :: ['NS3'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity10242 :: ('5894', 'Gene') :: ['NS5'] @entity779 :: ('MESH:D003715', 'Disease') :: ['Dengue', 'paired dengue']
@entity1 :: (9606,Species) :: ['Human']
