Histone acetyltransferase BmMOF inhibits the proliferation of the Bombyx mori nucleopolyhedrovirus by targeting Bmp53

Bombyx mori nucleopolyhedrovirus (BmNPV) infection is a critical disease in silkworms (Bombyx mori), yet the molecular mechanism underlying the defense of Bombyx mori against BmNPV infection remains elusive. The histone acetyltransferase MOF plays a crucial role in cellular stress response and apoptosis. Nevertheless, its function in Bombyx mori is yet to be fully elucidated. Here, we demonstrated that BmMOF positively regulates the resistance of silkworm BmN cells to BmNPV by targeting a Bombyx mori homolog of the apoptosis-inducing factor Bmp53. Overexpression of BmMOF led to the suppression of BmNPV proliferation and the enhancement of cellular antiviral responses, conversely, RNA interference targeting BmMOF promoted viral proliferation, resulting in an opposite effect. Additionally, the application of the acetyltransferase inhibitor MG149 and the mutated BmMOF acetyltransferase active site K257R revealed that BmMOF is capable of acetylating H4K16 in BmN cells, and its acetylation function plays a crucial role in inhibiting virus proliferation. Further analyses showed that BmMOF interacted with Bmp53 and catalyzes its acetylation, thereby inducing the apoptosismediated antiviral immune response in BmN cells upon infection with BmNPV. These findings provided a new molecular target for antiviral immunity and information for comprehending the mechanism of host-virus interaction in silkworms.