RNA Sequencing Reveals circRNA Expression Profiles in Chicken DF1 Cells Infected with H5N1 Influenza Virus

SIMPLE SUMMARY: H5N1 is a highly pathogenic avian influenza virus that seriously harms the poultry industry and public health worldwide. However, its pathogenesis is still not well understood. In this study, we analyzed the expression profile of circular RNAs (circRNAs) in H5N1-infected chicken embryo fibroblast (DF1) cells and found their expression to change more significantly as the infection was extended. Differentially expressed circRNAs were significantly enriched in terms relating to virus replication and immune response, suggesting that circRNAs play important roles in the pathogenesis of H5N1 infection. Our study provides new insights into the mechanisms underlying H5N1–host interaction. ABSTRACT: H5N1, a highly pathogenic avian influenza virus that is prevalent in Asia, seriously harms the poultry industry and global public health. However, its pathogenesis is still not well understood. Circular RNAs (circRNAs), a newly identified type of RNA, reportedly play crucial roles in various pathogenic processes. In this study, RNA sequencing was performed to analyze the expression profile of circRNAs in H5N1-infected chicken embryo fibroblast (DF1) cells. A total of 14,586 circRNAs were identified. The expression profiles of infected cells changed more significantly, relative to uninfected cells, as the infection period was extended; namely, 261, 626, and 1103 circRNAs exhibited differential expression in cells infected for 6 h, 12 h, and 20 h, respectively. GO and KEGG enrichment analysis revealed significant enrichment of the parental genes of the differentially expressed circRNAs for viral replication and immune response-related pathways, such as positive regulation of transcription from the RNA polymerase II promoter, positive regulation of I-kappaB kinase/NF-kappaB signaling, innate immune response, and ubiquitin protein ligase activity. In conclusion, we identified the expression profile of circRNAs in H5N1-infected chicken DF1 cells. Bioinformatic analyses of the dysregulated circRNAs suggest that circRNAs might play important roles in the pathogenesis of H5N1 infection, offering new insights into the mechanisms underlying H5N1–host interaction.