Functional Characterization of Spase12 as a Host Factor Contributing to Bombyx mori Nucleopolyhedrovirus Susceptibility in Silkworms

Bombyx mori is an important economic insect, and its production efficiency is seriously threatened by B. mori nucleopolyhedrovirus (BmNPV). A deeper understanding of host factors exploited during viral infection is crucial for developing disease-resistant silkworm strains. In the current study, we explored the function of Spase12, a subunit of the signal peptidase complex, in the silkworm's antiviral defense. The tissue expression profile showed that Spase12 is primarily expressed in the midgut and ovaries, and its expression was significantly upregulated in BmN cells and midgut tissues following BmNPV infection. Additionally, bioinformatics analyses predicted that Spase12 is a two-pass endoplasmic reticulum membrane protein, consistent with its role in protein processing and secretion. Moreover, RNAi-mediated knockdown of Spase12 significantly suppressed BmNPV replication, as evidenced by decreased VP39 expression. On the other hand, overexpression of Spase12 in BmN cells and in vivo experiments using a recombinant baculovirus system confirmed increased viral proliferation and DNA load in the midgut of infected silkworm larvae. Together, these findings established a pro-viral role for Spase12 during BmNPV infection, likely hijacked by the virus to facilitate its replication. This study offers novel insights into host-virus interactions in silkworms and highlights Spase12 as a potential molecular target for breeding BmNPV-resistant B. mori strains.