Analysis and identification of circRNA-regulated ceRNA networks associated with the virulence differences between PRV...

The virulence and replication of PRV are not only regulated by the virulence genes gE or gI, but also related to host circRNA, miRNA, and lncRNA. Circular RNAs (circRNAs) fulfill a diverse array of biological functions. However, the functions of circRNAs in PRV infections by attenuated and virulent strains are not yet fully elucidated. In this study, the circRNA expression profiles of the PRV virulent strain FA and attenuated strain FB were established and analyzed by high-throughput sequencing technology. A ceRNA network was established utilizing differentially expressed circRNAs (DE circRNAs), and their biological functions of these circRNAs were subsequently predicted.

We found that 4 DE circRNAs (animalcirc_014421, animalcirc_004115, animalcirc_010807, and animalcirc_000091) in infections with PRV virulent and attenuated strains mediated the interactions among circRNAs, miRNAs, and mRNAs within the ceRNA network. The target genes of these DE circRNAs were associated with lysosome and apoptosis-related biological processes. Notably, target genes such as PiK3rl and Pou2f1 were enriched in the Herpes simplex virus 1 infection pathway. The findings indicate that these DE circRNAs could be crucial in the infection process of Herpesviruses.

circRNAs may contribute to the differences in virulence and replication between the PRV FA strain and attenuated FB strain through pathways such as apoptosis and lysosomal regulation. This research provides novel insights into the molecular mechanisms by which host circRNAs modulate the phenotypic disparities between PRV virulent and attenuated strains.