Time-Course Transcriptomic Analysis of Early Host Responses to Oral SfMNPV Challenge in Spodoptera frugiperda Larval Midgut

The fall armyworm (Spodoptera frugiperda) is a major global migratory pest. Its increasing insecticide resistance poses a severe threat to food security. Developing biopesticides such as SfMNPV is critical for sustainable control. Nevertheless, the early molecular mechanisms underlying the S. frugiperda midgut response to oral SfMNPV challenge remain poorly understood. This study utilized high-throughput transcriptome sequencing to systematically characterize the dynamic transcriptional profiles of the larval midgut at 1, 12, and 24 h after oral SfMNPV inoculation. Results showed that the midgut transcriptional response to SfMNPV is time and stage-specific. During this period, the physical midgut barrier underwent remodeling, with core components of the peritrophic matrix downregulated at 1 h, followed by the basal lamina at 12 h, alongside the activation of cytoskeleton genes during 12–24 h. Concurrently, sustained endoplasmic reticulum stress, autophagy, and ubiquitin system responses occurred from 12 to 24 h. At the metabolic level, the defense system exhibited a functional succession, shifting from ABC transporters and UDP-glycosyltransferases at 1 h to glutathione S-transferases and superoxide dismutase at 12–24 h. Additionally, the midgut tissue exhibited a cascade transition from pro-apoptotic signaling at 1 h to compensatory regenerative repair mediated by the Wnt, mTOR, and Hippo pathways at 12–24 h. This study elucidates the molecular process of barrier damage, homeostatic imbalance, and tissue remodeling during early oral SfMNPV challenge. These findings provide a global perspective on baculovirus-host interactions and establish a theoretical foundation for designing novel biopesticides targeting the midgut interaction.