Forkhead-box O (FoxO) is the primary transcriptional effector of the insulin-like signaling pathway that enhances gluconeogenesis through transcriptional activation of PEPCK and G6Pase in mammals. We have previously demonstrated the involvement of phosphoenolpyruvate carboxykinase (BmPEPCK-2) in antiviral immunity against the multiplication of Bombyx mori nuclearpolyhedrosisvirus (BmNPV) in silkworm. Therefore, we speculated that BmFoxO might suppress BmNPV by regulating the expression of PEPCK in silkworm. In the present study, we found that the expression of BmFoxO decreased after BmNPV infection in Bombyx mori; this finding was consistent with BmPEPCK-2 expression. In addition, the expression of BmFoxO was altered, and it was found that reduced expression of BmFoxO (dsBmFoxO) downregulated the expression of BmPEPCK-2 and increased the viral fluorescence and content in silkworm embryonic cell line BmE cells, and vice versa. BmFoxO could upregulate the expression of BmPEPCK-2 by binding to the BmPEPCK-2 promoter. Moreover, overexpression of BmFoxO significantly increased the expression of autophagy genes ATG6/7/8 after infection with BmNPV, consistent with BmPEPCK-2. These results indicate that BmNPV downregulates transcription factor BmFoxO to elevate virus infection, and BmFoxO overexpression upregulates BmPEPCK-2 expression and enhances silkworm antiviral resistance.

Forkhead-box O (FoxO) 是胰岛素样信号通路的主要转录效应物，通过转录激活哺乳动物的 PEPCK 和 G6Pase 来增强糖异生。我们之前已经证明了磷酸烯醇丙酮酸羧激酶 ( BmPEPCK-2 ) 参与了家蚕中家蚕核型多角体病毒 (BmNPV)增殖的抗病毒免疫。因此，我们推测BmFoxO可能通过调控家蚕PEPCK的表达来抑制BmNPV 。本研究发现家蚕感染BmNPV后BmFoxO的表达降低；这一发现与BmPEPCK-2一致表达。此外，BmFoxO的表达发生了改变，发现BmFoxO（dsBmFoxO）表达降低，在家蚕胚胎细胞系BmE细胞中下调BmPEPCK-2的表达，增加病毒荧光和含量，反之亦然。BmFoxO可以通过与BmPEPCK-2启动子结合上调BmPEPCK-2的表达。此外，BmFoxO的过表达显着增加了BmNPV 感染后自噬基因ATG6 /7/8 的表达，与BmPEPCK-2一致. 这些结果表明，BmNPV 下调转录因子BmFoxO以增强病毒感染，而BmFoxO过表达上调BmPEPCK-2表达并增强家蚕抗病毒性。