Abstract

VcircRNA_000048 is a viral circRNA (vcircRNA) derived from the region 164 - 1245 nt on the genomic dsRNA S5 segment (GQ294468.1) of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). Our previous studies indicated that BmCPV replication is suppressed by the activation of the NF-κB/autophagy pathway through the interaction of vsp21 translated by vcircRNA_000048 with ubiquitin carboxyl-terminal hydrolase (UCH). However, it remains unknown whether vcircRNA_000048 can hijack host metabolism through interaction with microRNAs (miRNAs). In this study, we found that vcircRNA_000048 upregulated methyltransferase-like 20 (METTL20) expression by acting as a sponge for the silkworm miRNA bmo-miR-2753, which leads to the inhibition of electron transfer flavoprotein β-subunit (ETFβ) gene expression and an increase in the trimethylation level of ETFβ. Furthermore, we demonstrated that vcircRNA_000048 damages mitochondria, reduces energy production, represses locomotor-related gene expression,and restrains BmCPV replication by promoting the trimethylation of ETFβ via the vcircRNA_000048-bmo-miR-2753-METTL20 regulatory axis. These findings revealed the mechanisms by which viral circRNAs affect both host energy production and viral replication, offering new insights for potential therapeutic strategies.