Dual functions of the Aedes aegypti ecdysone receptor in dengue virus replication and reproduction control

Abstract Background The ecdysone receptor (EcR) is a central regulator of mosquito physiology, best known for its role in vitellogenesis. However, its contribution to antiviral defense and dengue virus (DENV) replication in Aedes aegypti remains poorly understood. Methods RNA interference was used to silence Aedes aegypti EcR (AaEcR). Effects on DENV replication, immune gene expression, ovarian development, vitellogenin (Vg) synthesis, and target of rapamycin (TOR) pathway activity were assessed using molecular, cellular, and phenotypic analyses. Results Silencing AaEcR markedly suppressed DENV replication, viral protein expression, and virion production. These antiviral effects coincided with increased expression of antimicrobial peptides and activation of innate immune pathways, indicating that AaEcR facilitates viral replication by dampening host defenses. In addition, AaEcR proved essential for reproductive output. Knockdown impaired ovarian development, reduced follicle size and number, and lowered egg production by ~30%, although egg viability was unaffected. At the molecular level, AaEcR depletion strongly reduced Vg transcription and protein abundance, along with decreased phosphorylation of S6 kinase, suggesting that AaEcR promotes fecundity through both transcriptional activation and TOR-Vg signaling. Conclusions AaEcR functions as a dual regulator of mosquito biology, suppressing antiviral immunity while enhancing reproductive output. This tradeoff between immunity and fecundity highlights AaEcR as a promising molecular target for vector control. Disrupting EcR signaling could simultaneously reduce mosquito population size and limit arboviral transmission, offering a potential strategy for integrated management of mosquito-borne diseases. Graphical Abstract