STRUCTURAL AND NONSTRUCTURAL PROTEIN DIVERGENCE CORRELATES WITH STRAIN SPECIFIC VECTOR COMPETENCE FOR ZIKA VIRUS
Background:Zika virus (ZIKV) has become a significant global health threat, with particular attention given to the Asian-lineage strains due to their association with major epidemics and neurological complications. In contrast, African lineages have been less extensively studied, and their transmission dynamics in Neotropical Aedes aegypti remain poorly characterized despite their central role in ZIKV evolutionary history.Methods:We assessed the transmission efficiency of Mexican Ae. aegypti populations orally exposed to blood meals containing either Old-World ZIKV (Dakar) or Neotropical (Honduras) strains. Infection, dissemination, and transmission rates were evaluated, and viral genome copies were quantified in midgut, body, and saliva tissues. Transcriptomic profiling via Illumina sequencing was performed on whole mosquitoes from each treatment group to identify differentially expressed genes (DEGs) and enriched functional pathways.Results:Infection rates were similar between strains, but dissemination and transmission were significantly higher for the Neotropical strain. Viral genome copies were also significantly elevated in all tissues for the Neotropical strain. Whole-genome sequencing identified nonsynonymous substitutions in the Neotropical strain affecting the Envelope (E), NS1, and NS2A proteins, whereas the Old-World isolate harbored a single NS2A substitution. Neotropical ZIKV infection was associated with suppression of immune effectors and peritrophic matrix remodeling genes. Functionally, infection did not alter secondary blood feeding success but imposed significant strain-specific reproductive costs.Conclusions:Mexican Ae. aegypti exhibit markedly higher competence for Neotropical ZIKV, associated with differences in viral replication dynamics and host gene modulation. These findings highlight viral lineage as a key determinant of vector competence, with implications for predicting transmission risk in endemic regions.