circEgg inhibits BmCPV infection by regulating the transition between H3K9me3 and H3K9ac

Abstract

Our previous study demonstrated that the expression level of circRNA circEgg, which is encoded by histone-lysine N-methyltransferase eggless (BmEgg), is responsive to Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) infection in the silkworm. However, the precise relationship between BmCPV infection and circEgg remains unclear. In this study, we observed that the expression level of circEgg in both the midguts and cultured BmN cells significantly increased after BmCPV infection, while the expression of its host gene, BmEgg, exhibited an opposite trend. Transient expression experiments revealed that circEgg acts to inhibit BmCPV infection. Additionally, Western blot analyses indicated that BmCPV infection leads to a downregulation of histone 3 lysine 9 trimethylation (H3K9me3) and an upregulation of histone 3 lysine 9 acetylation (H3K9ac). Notably, the levels of H3K9ac and H3K9me3 were found to be positively and negatively correlated with circEgg expression, respectively, suggesting that circEgg may regulate the transition between H3K9me3 and H3K9ac. Mechanistically, we discovered that circEgg inhibits BmCPV infection by enhancing the H3K9ac level through the circEgg-bmo-miR-3391-5p-histone deacetylase Rpd3 network, while simultaneously reducing the H3K9me3 level via the circEgg-encoded protein circEgg-P122. Collectively, these findings indicate that circEgg plays a crucial role in inhibiting BmCPV infection by modulating the balance between H3K9me3 and H3K9ac.