Differential host circRNA expression profiles in human lung epithelial cells infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging and highly pathogenic coronavirus that causes coronavirus disease (COVID-19), and might even lead to death. Circular RNAs (circRNAs), a new type of RNAs, are implicated in viral pathogenesis and host immune responses. However, their dynamic expression patterns and functions during SARS-CoV-2 infection remain to be unclear. We herein performed genome-wide dynamic analysis of circRNAs in human lung epithelial cells infected with SARS-CoV-2 at four time points. A total of 6118 circRNAs were identified at different genomic locations, including 5641 known and 477 novel circRNAs. Notably, a total of 42 circRNAs were significantly dysregulated, wherein 17 were up-regulated and 25 were down-regulated following infection at multiple phases. The gene ontology and KEGG enrichment analyses revealed that the parental genes of circRNAs were mainly involved in immune and inflammatory responses. Further, the RNA binding protein (RBP) prediction analysis indicated that the dysregulated circRNAs could regulate mRNA stability, immunity, cell death by binding specific proteins. Additionally, the circRNA-miRNA-gene network analysis showed that circRNAs indirectly regulated gene expression by absorbing their targeted miRNAs. Collectively, these results shed light on the roles of circRNAs in virus-host interactions, facilitating future studies on SARS-CoV-2 infection and pathogenesis.