The circRNA circSIAE Inhibits Replication of Coxsackie Virus B3 by Targeting miR-331-3p and Thousand and One Amino-Acid Kinase 2

Abstract

Coxsackie virus B3 (CVB3), an enterovirus, is the main pathogen causing viral myocarditis, pericarditis, hepatitis and other inflammation-related diseases. Non-coding RNAs with a closed loop molecular structure, called circular RNAs (circRNAs), have been shown to be involved in multiple virus-related processes, but roles and mechanisms in CVB3 infection have not been systematically studied. In this study, when HeLa cells were infected with CVB3, the expression of hsa_circ_0000367 (circSIAE) was significantly decreased as demonstrated by real-time quantitative PCR assays. We found that circSIAE downregulated the expression of miR-331-3p through direct binding and inhibited the replication of CVB3 in HeLa and 293T cells. The analysis of signals downstream of miR-331-3p suggested that miR-331-3p promotes CVB3 replication, viral plaque formation and fluorescent virus cell production through interactions with the gene coding for thousand and one amino-acid kinase 2 (TAOK2). In conclusion, this study found that circSIAE can target TAOK2 through sponge adsorption of miR-331-3p to inhibit the replication and proliferation of CVB3 virus, providing an early molecular target for the diagnosis of CVB3 infection.

Circular RNA circ_0076631 promotes coxsackievirus B3 infection through modulating viral translation by sponging miR-214-3p

“…To date, little is known about the association between circRNAs and enterovirus infection. CircSIAE is an exception that it can act as a sponge for miR-331-3p and inhibit CVB3 infection indirectly by up-regulating host’s TAOK2 expression ( Yang et al, 2022 ). Our finding provides another example of circRNA interfering enterovirus infection in a much more direct way.…”

“…To date, the involvement of circRNAs in CVB replication remains unknown. Only hsa_circ_0000367 (circSIAE) has been reported to inhibit CVB3 replication by targeting cellular TAOK2 (thousand and one amino-acid kinase 2) through sponge adsorption of miR-331-3p ( Yang et al, 2022 ).…”

Host Combats IBDV Infection at Both Protein and RNA Levels

“…Lines of evidence indicate that circRNAs play a role in various human disorders, and most of them are correlated with tumor progression or repression [ 151 , 152 ]. In recent years, a growing number of studies reported that circRNAs also participated in virus–host interaction [ 153 , 154 ]. In the area of IBDV infection, there was only one report that showed the differential expression profiles of circRNAs, and it indicated that 63 circRNAs were upregulated and 80 downregulated [ 144 ].…”

Expression Profiles of Differentially Expressed Circular RNAs and circRNA–miRNA–mRNA Regulatory Networks in SH-SY5Y Cells Infected with Coxsackievirus B5

“…Network. CircRNAs are known to offset miRNA-mediated gene regulation by acting as miRNA sponges [8]. To identify the critical roles of expressed circRNAs in CVB5-infected SH-SY5Y cells, a circRNA-miRNA-mRNA interaction network was established.…”

“…With the development of RNA-seq, many research groups have conducted studies to reveal the expression profiles of circRNA after the viral infection and better understand their pathogenesis [6,7]. So far, large amounts of circRNAs have been successfully identified in a variety of virus infection models like Coxsackie Virus B3, Marek's disease virus, and Hepatitis B virus [8][9][10]. In addition, circRNAs have been shown to be widely expressed from humans to viruses as potential regulators of microRNAs (miRNAs) and RNAbinding proteins (RPBs) [11].…”