Circular RNAs (circRNAs), a new class of regulators of gene expression, are involved in diverse physiological and pathogenic processes. However, their role in cellular responses to virus infection is yet unclear.

In a recent study, a human lung fibroblast cell line was infected or mock infected by herpes simplex virus 1 (HSV-1). Deep RNA sequencing was used to profile the global changes in circRNAs, genes, and miRNAs following HSV-1 infection. Altered circRNAs, genes, and miRNAs were validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). An integration analysis of circRNAs, genes, and miRNAs was applied to investigate the putative function of the dysregulated circRNAs.

A total of 536 circRNAs, 3,885 genes, and 207 miRNAs were significantly dysregulated after HSV-1 infection. An integration analysis of circRNAs, genes, and miRNAs revealed the alleged involvement of dysregulated circRNAs in cellular responses to HSV-1 infection via the circRNA-miRNA-gene regulatory axis. These genes regulated by circRNAs were enriched to NOD-like receptor/JAK-STAT signaling pathway, and pathways of apoptosis, cell cycle progression, and cell death, all of which may be implicated in the viral pathogenesis and cellular immunity.

These data present a comprehensive view for circRNAs induced by HSV-1 and their interplay with miRNAs and genes during HSV-1 infection, thus offering new insights into the mechanisms of interactions between HSV-1 and the host.

LC Sciences

Dysregulated genes after HSV-1 infection. (A) Heatmap of differentially expressed genes induced by HSV-1 in KMB17 cells. Red color indicates a high expression level, and blue color indicates a low expression level. (B) MA-plots show transcriptome dynamics of both HSV-1 infected and uninfected KMB17 cells. The log2 fold-change in the expression (Y-axis) was plotted against the mean of normalized counts (X-axis). (C) Validation of dysregulated genes by RT-qPCR. qPCR data was normalized against the human gene GAPDH. Differences among groups were analyzed using the t-test (two-tailed and unpaired). A P-value of < 0.05 (*), < 0.01 (**) or < 0.001 (***) was considered statistically significant.


J. Shi, N. Hu, L. Mo, Z. Zeng, J. Sun, Y. Hu (2018) Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection Cell Physiol Biochem 47:2031–2045 doi: 10.1159/000491471 [article]

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