Bombyx mori BmLis1 inhibits BmNPV replication by promoting the cell cycle G2/M progression

Lissencephaly-1 (Lis1) is a highly conserved cytoplasmic dynein regulator found in eukaryotes. It is involved in regulating processes such as cell proliferation, spindle orientation, nuclear migration, and microtubule-dependent transport. Baculovirus frequently hijacks these cellular processes to facilitate infection and replication, whether Lis1 has a role during Baculovirus infection remains unexplored. This study found that Bombyx mori nucleopolyhedrovirus (BmNPV) infection downregulates Bombyx mori Lis1 (BmLis1) expression, suggesting its involvement in regulating viral replication. To investigate the function of BmLis1 during BmNPV infection, we performed flow cytometry, Western blotting, and qRT-PCR analyses following BmLis1 overexpression and knockout. All results demonstrated that BmLis1 significantly suppresses BmNPV replication, as evidenced by changes in the expression levels of EGFP-positive cells, VP39 protein, and key viral genes. Meanwhile, we demonstrated that BmLis1 significantly improves survival and inhibits viral proliferation in the BmLis1-OE transgenic line. Moreover, we proved that BmLis1 inhibits viral replication by upregulating BmCyclin B expression, thereby reducing the proportion of cells in the G2/M phase of the cell cycle. More importantly, we found that BmNude1, an interacting protein of BmLis1, acts synergistically with BmLis1 to influence BmNPV proliferation by modulating BmCyclin B expression and G2/M phase progression. Collectively, these findings provide the first evidence that BmLis1 is a crucial host restriction factor against BmNPV infection that involves regulating cell cycle progression. These findings provide novel insights into the molecular mechanisms by which host factors combat baculovirus infection through modulation of the cell cycle.