Nicotinic Acetylcholine Receptor Alpha6 Contributes to Antiviral Immunity Via IMD Pathway in

Currently, insecticides that target nicotinic acetylcholine receptors (nAChR) are widely used. Studies on the sublethal effects of insecticides have found that they can affect the amount of virus in insects. The mechanism by which insecticides affect insect virus load remain unclear. Here, we show that nAChR targeting insecticide can affect viral replication through the immune deficiency (IMD) pathway. We demonstrate that a low dose of spinosad (6.8 ng/mL), acting as an antagonist to nicotinic acetylcholine receptor α6 (Dα6), significantly elevates Drosophila melanogaster sigmavirus (DMelSV) virus titers in adults of . Conversely, a high dose of spinosad (50 ng/mL), acting as an agonist to Dα6, substantially decreases viral load. This bidirectional regulation of virus levels is absent in -knockout flies, signifying the specificity of spinosad's action through . Furthermore, the knockdown of results in decreased expression of genes in the IMD pathway, including , , , and downstream antimicrobial peptide genes and , indicating a reduced innate immune response. Subsequent investigations reveal no significant difference in viral titers between mutant flies and - double mutants, suggesting that the IMD pathway's role in antiviral defense is dependent on . Collectively, our findings shed light on the intricate interplay between nAChR signaling and the IMD pathway in mediating antiviral immunity, highlighting the potential for nAChR-targeting compounds to inadvertently influence viral dynamics in insect hosts. This knowledge may inform the development of integrated pest management strategies that consider the broader ecological impact of insecticide use.