A laboratory-adapted and a clinical isolate of dengue virus serotype 4 differently impact Aedes aegypti life-history traits relevant to vectorial capacity.

UNLABELLED: Dengue virus cases are on the rise globally, and strategies to control its primary vector, the mosquito Aedes aegypti, represent a promising approach. However, the interaction between virus serotypes and genotypes with Ae. aegypti is poorly characterized in terms of life-history traits related to vector capacity and mosquito disease tolerance. Here, we infected Ae. aegypti with two phylogenetically distant strains of dengue virus serotype 4 genotype II: a laboratory-adapted strain, DENV4-TVP/360, and a recent clinical strain isolated from southern Brazil, DENV4-LRV 13/422. These strains exhibit 26 amino acid differences in their sequences. We assessed various life-history traits of Ae. aegypti, including mortality, fecundity, fertility, and induced flight capacity, as well as vector competence-related parameters, such as infection intensity and prevalence, following exposure to different viral concentrations. We found that while neither strain significantly reduced mosquito lifespan, infection prevalence was highly influenced by the initial dose of DENV4-TVP/360. In contrast, the infectious prevalence of DENV4-LRV 13/422 was smaller (~40% at 14 days post-infection [DPI]), regardless of the initial virus titers. The DENV4-TVP/360 strain also enhanced mosquito-induced flight capacity at early (1 day post-infection) and late (21 DPI) time points, when dispersion is critical for vector competence. On the other hand, DENV4-LRV13/422 reduced Ae. aegypti fertility. A better understanding of how arbovirus strains influence mosquito life-history traits connected to disease spread is critical in public health efforts to mitigate arbovirus outbreaks that are focused on the mosquito vector.

IMPORTANCE: As dengue virus (DENV) cases rise globally, vector control strategies targeting Aedes aegypti remain essential to public health. The effectiveness of these interventions depends on understanding how viral strains interact with mosquito biology. We show that two phylogenetically distinct DENV serotype 4 strains-one laboratory-adapted, one recently isolated-differentially affect Ae. aegypti traits, such as fertility, flight capacity, and infection dynamics. These traits are linked to mosquito fitness and vector competence, and our results show that sequence variation can shape mosquito-virus interactions. The lab strain enhanced flight capacity at key time points, potentially aiding transmission, while the clinical isolate reduced fertility independently of viral dose. Infection prevalence and sensitivity to viral dose also differed between strains. These findings highlight how viral genotype influences mosquito performance and transmission potential. Incorporating viral genetic diversity into arbovirus studies can improve disease spread models and inform mosquito-based control strategies.