CircRNA0857 acts as an miRNA sponge to promote Newcastle disease virus replication via modulating autophagy

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs widely expressed across diverse organisms. These molecules are involved in various biological processes, such as transcriptional and post-transcriptional regulation, protein scaffolding, and acting as miRNA sponges. Newcastle disease virus (NDV) replicates and proliferates in a variety of cells, inducing severe organelle stress damage, autophagy, and even cell death. Previous studies have reported that NDV hijacks and uses autophagy to promote its replication and proliferation. However, the involvement and regulatory mechanisms of circRNAs in this process remain largely unexplored. The present study aimed to identify novel circRNAs that modulate NDV replication through autophagy and elucidate their underlying mechanisms. Our findings revealed that circRNA0857 was significantly upregulated in NDV-infected cells. Functional assays showed that silencing circRNA0857 markedly inhibited NDV replication, while its overexpression enhanced viral replication. Mechanistic analyses demonstrated that circRNA0857 functions as a "miRNA sponge," specifically targeting and sequestering miR1709 and miR1746. These miRNAs were found to regulate the expression of ATG3 and ATG7, respectively, two key autophagy-related genes in the autophagy pathway. By sponging miR1709 and miR1746, circRNA0857 upregulates the expression of ATG3 and ATG7, thereby enhancing autophagy and promoting NDV infection. This study is the first to identify circRNA0857 as a critical regulator in NDV infection, elucidating its role in enhancing NDV-induced autophagy via the miR1709/ATG3 and miR1746/ATG7 signaling axes. These findings significantly advance our understanding of how circRNAs regulate viral infections and provide novel insights into the molecular mechanisms underlying NDV replication.IMPORTANCECircular RNAs (circRNAs), as endogenous non-coding RNAs, are widely involved in various biological processes, particularly in the regulatory modulation of miRNA functions. Newcastle disease virus (NDV) can replicate in a variety of cells and promote its proliferation by hijacking and utilizing autophagy. In this study, we screened for novel circular RNAs that regulate NDV replication through modulating host autophagy and identified circRNA0857 as a key regulator of NDV infection. It enhances autophagy and promotes viral replication by acting as a "miRNA sponge," simultaneously targeting the two signaling axes miR1709/ATG3 and miR1746/ATG7. This research fills a gap in understanding how circRNAs regulate NDV-induced autophagy and provides a new perspective for understanding the interactions between host non-coding RNAs and viruses. This finding deepens our understanding of the pathogenic mechanisms of NDV and offers potential molecular targets for the development of antiviral strategies based on circular RNAs or miRNAs.