The mechanism by which infection by Bombyx mori cytoplasmic nucleopolyhedrosis virus (BmCPV) causes autophagy has not been studied in detail. Herein we have observed by electron microscopy that infection with BmCPV causes autophagosome and mitochondrial structure damage in Bombyx mori midgut. In BmN cells infected with BmCPV and expressing eGFP-LC3, fluorescence spots and LC3-II levels increased, suggesting that BmCPV infection causes autophagy. Autophagy inducer rapamycin (Rap) and autophagy inhibitor 3-methyladenine (3-MA) were used to monitor the effects of mitophagy on BmCPV proliferation. It was found BmCPV proliferation to be promoted by mitophagy. Transient transfection experiments in cultured BmN cells showed that mitophagy can be triggered by expression of BmCPV structural protein VP4. Moreover, VP4 caused upregulation of p-Drp1, PINK1 and Parkin proteins in the mitophagy pathway and downregulation of mitochondrial membrane protein Tom20. Furthermore, interaction between VP4 with Tom40 was confirmed by Co-IP, western blot and colocalization experiment, and overexpression of Tom40 reduce the level of mitochondrial autophagy induced by VP4. These results suggested that VP4 induced PINK1-Parkin-mediated mitophagy interacting with Tom40. These findings deepen our understanding of the interaction between BmCPV and silkworm and also provide a molecular target for screening anti-BmCPV drugs.

家蚕细胞质核多角体病毒（BmCPV）感染引起自噬的机制尚未得到详细研究。在此，我们通过电子显微镜观察到感染 BmCPV 会导致家蚕自噬体和线粒体结构受损中肠。在感染 BmCPV 并表达 eGFP-LC3 的 BmN 细胞中，荧光斑点和 LC3-II 水平增加，表明 BmCPV 感染引起自噬。自噬诱导剂雷帕霉素 (Rap) 和自噬抑制剂 3-甲基腺嘌呤 (3-MA) 用于监测线粒体自噬对 BmCPV 增殖的影响。发现线粒体自噬促进了BmCPV的增殖。在培养的 BmN 细胞中进行的瞬时转染实验表明，线粒体自噬可以通过 BmCPV 结构蛋白 VP4 的表达来触发。此外，VP4 引起线粒体自噬途径中 p-Drp1、PINK1 和 Parkin 蛋白的上调和线粒体膜蛋白 Tom20 的下调。此外，通过 Co-IP、蛋白质印迹和共定位实验证实了 VP4 与 Tom40 之间的相互作用，和 Tom40 的过表达降低了 VP4 诱导的线粒体自噬水平。这些结果表明 VP4 诱导 PINK1-Parkin 介导的线粒体自噬与 Tom40 相互作用。这些发现加深了我们对BmCPV与家蚕相互作用的认识，也为筛选抗BmCPV药物提供了分子靶点。