Current insights and future perspectives on the antiviral defense of Bombyx mori: molecular mechanisms and strategies against Bombyx mori nucleopolyhedrovirus (BmNPV)

Abstract Bombyx mor i, also known as the silkworm, is a lepidopteran species of high economic importance and a crucial model for insect antiviral immunity. However, its cultivation is often jeopardized by the highly virulent pathogen Bombyx mori nucleopolyhedrovirus (BmNPV), leading to more than 60% loss in cocoon yield. In the absence of effective antiviral therapeutics, developing virus-resistant B. mori strains is considered the most sustainable long-term solution. A critical analysis of the molecular mechanisms, genetic determinants, and cellular defenses underlying B. mori resistance to BmNPV is therefore essential. Recent studies have revealed complex host–pathogen interactions, identifying key resistance genes, regulatory noncoding RNAs, and major signaling pathways. This review goes beyond existing summaries by providing an integrative and critical framework that links molecular mechanisms of antiviral immunity with emerging multi-omics and genome-editing approaches. We systematically connect midgut barrier defenses, viral entry mechanisms, and key immune signaling pathways-including Toll, Imd, JAK/STAT, RNA interference, the phenoloxidase cascade, and autophagy-within a unified host–pathogen interaction model organism. Importantly, we highlight underexplored areas such as the dual role of autophagy in viral propagation, the polygenic architecture of resistance, and the regulatory functions of noncoding RNAs. Unlike previous reviews, we emphasize unresolved contradictions, lack of functional validation, and tissue-specific immune limitations. Furthermore, we propose a forward-looking strategy that integrates comparative genomics, single-cell omics, and CRISPR/Cas9-based tools to translate mechanistic insights into durable antiviral resistance.