The gut microbiome-immunity-virus axis in lepidopteran antiviral defense.

The gut microbiota forms a competitive biological barrier against enteric pathogens and may also modulate antiviral immunity and disease prevention. This review presents recent advances demonstrating the tripartite model of the gut microbiome-immunity-virus axis in lepidopteran insects. Emerging evidence indicates that their gut microbiota regulates antiviral immunity through context-dependent mechanisms shaped by host species identity, microbial community composition, and strain-specific differences in viral resistance. Rather than acting as a uniformly protective factor, gut microbes fine-tune the local immune environment chiefly through antimicrobial peptide induction, modulation of prophenoloxidase/melanization, Duox/reactive oxygen species regulation, and maintenance of epithelial homeostasis. Although RNA interference, stimulator of interferon gene-related, and Janus kinase/signal transducer and activator of transcription signaling are established antiviral pathways in Lepidoptera, their direct regulation by gut microorganisms during viral infection remains elusive. These microbiota-conditioned immune states can either restrict viral replication and maintain gut barrier integrity or, conversely, favor virus pathogenesis when infection disrupts gut homeostasis, drives dysbiosis, or suppresses key antiviral effectors. Furthermore, strain-specific microbiome signatures correlate with differential viral resistance in susceptible and resistant hosts. By positioning the gut microbiome as a crucial immunological interface, this review integrates symbiosis biology into insect antiviral immunity and highlights microbiome-informed opportunities for sustainable pest management and the protection of beneficial insects.