An NF‐κB‐regulated cytokine enhances the antiviral resistance of silkworm, Bombyx mori

Abstract Insect NF‐κB‐like factor, Relish, is activated by viral infection and induces the production of antiviral proteins. In this study, we performed a transcriptomic analysis of BmE cells expressing the active form of BmRelish (BmRelish act ) and identified BmVago‐like as the most strongly‐induced secreted‐protein. Expression of BmVago‐like was specifically triggered by Bombyx mori Nucleo Polyhedro Virus (BmNPV) infection and regulated by BmSTING‐BmRelish pathway. Incubating the fresh culture of cells with supernatant medium of BmVago‐like expressing cells or recombinant BmVago‐like protein (rBmVago‐like) significantly increased antiviral resistance. On the contrary, reducing the expression of Bmvago‐like by RNA interference (RNAi) in BmE cells as well as in silkworm larvae impaired antiviral response. Furthermore, we constructed transgenic silkworm line over‐expressing BmVago‐like (BmVago‐like OV ) and found they had markedly lower viral load and higher survival rate after BmNPV infection compared with the wild‐type control. Co‐immunoprecipitation assay showed Bmintegrin β1 interacts with BmVago‐like and it was involved in BmVago‐like mediated antiviral response. Finally, we found the expression level of signalling molecules in the JAK–STAT pathway increased in rBmVago‐like‐treated cells and BmVago‐like OV silkworm larvae but decreased in RNAi‐treated cells. In summary, our research uncovered an inducible antiviral response in silkworm mediated by cytokine BmVago‐like, which is the downstream effector of BmSTING‐BmRelish pathway and functions as an antiviral cytokine.