Cell autophagy promotes nucleopolyhedrovirus infection in the fall armyworm

Pathogens, such as nucleopolyhedroviruses (NPVs), are promising biological control agents for lepidopteran pests to protect crops. However, a major drawback, their field application is limited by slower virulence compared with chemical insecticides. Modulating host pathways to enhance viral infectivity offers a potential strategy for improving NPV-based biocontrol. In this study, the expression level of NADH:ubiquinone oxidoreductase core subunit S8 (Ndufs8) was upregulated in the insect midgut following Spodoptera frugiperda NPV (SfNPV) infection. Silencing Ndufs8 impaired mitochondrial function, increased oxidative stress, and activated autophagy, but had no significant adverse effects on larval development and survival. The Ndufs8-autophagy cascade subsequently promoted SfNPV replication in insects. Co-feeding larvae with SfNPV and nanocarrier-delivered double-stranded RNA targeting Ndufs8 (dsNdufs8) accelerated insect death compared with the virus alone, demonstrating the enhanced virulence. Furthermore, bacterially expressed short hairpin RNA against Ndufs8 (shNdufs8), followed with nanocarrier delivery, achieved effective gene silencing and increased insect mortality comparable to synthetic dsNdufs8, supporting the potential field application for scalable RNA delivery. Our findings elucidate the function of a host responsive gene in the virus-host interaction. The combined use of dsNdufs8/shNdufs8 with SfNPV highlights a practical and scalable strategy to integrate RNA interference with pathogens to improve the biocontrol efficacy against insect pests.