Bombyx mori IML-2 modulates intracellular reactive oxygen species levels and downregulates glycolytic flux to inhibit viral infection

C-type lectins (CTLs) are crucial pattern recognition receptors in invertebrate innate immunity. Previous studies revealed that the silkworm (Bombyx mori) C-type lectin gene BmIML-2 suppresses Nucleopolyhedrovirus (BmNPV) proliferation through apoptotic signaling pathways. However, whether BmIML-2 regulates oxidative stress and glycolysis during viral infection remains unknown. In this study, we found that BmIML-2 was significantly upregulated in resistant strains upon BmNPV infection. Gain- and loss-of-function assays indicated that BmIML-2 suppressed viral replication by enhancing oxidative stress and inhibiting glycolytic metabolism. Mechanistically, BmIML-2 promotes reactive oxygen species (ROS) accumulation, modulates oxidative stress-related gene expression, disrupts mitochondrial membrane potential, downregulates glycolytic pathway genes, and reduces ATP production. These findings uncover a novel antiviral mechanism of C-type lectins through coordinated regulation of oxidative stress and metabolic reprogramming, providing insights into insect antiviral immunity.