Bombyx mori nucleopolyhedrovirus F-like protein Bm14 is a factor for viral-induced cytopathic effects via regulating oxidative phosphorylation and cellular ROS levels.

Bombyx mori nucleopolyhedrovirus (BmNPV) is highly pathogenic to Bombyx mori, silkworm, which causes serious cytopathic effects (CPEs) during infection. However, the role of viral protein in the virus-induced CPEs remains unclear. Here, we discovered that BmNPV infection induced severe CPEs including titer-dependent cell floating and changes in cellular surface morphology. Further explorations revealed the involvement of F-like protein (Bm14), a viral envelope protein, in inducing cytotoxicity and detachment of adherent BmN cells, and its disruption significantly impaired the virus infection-mediated CPEs. Intriguingly, transcriptomic analysis identified the tight association of Bm14 deletion with the activation of cellular oxidative phosphorylation pathway, consistent with the elevated mitochondrial membrane potential (MMP) levels and ATP concentrations as well as reduced ROS levels. Collectively, our results characterized for the first time the novel role of Bm14 in accelerating viral-induced cytopathogenicity via suppressing the cellular oxidative phosphorylation levels and upregulating the ROS levels.