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

Qingru Yang,Tingjun Liu,Hua Wang,Yuhan Li,Hongxing Shen,Xiaorong Qiao,Yan Wang

doi:10.3389/fcimb.2021.779919

Qingru Yang, Tingjun Liu + Show 5 more

Open Access

https://doi.org/10.3389/fcimb.2021.779919

Copy DOI

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.

Highlights

Coxsackievirus B3 (CVB3) is a member of the Picornaviridae family in the genus Enterovirus
Total RNA of Human cervical cancer cells (HeLa) cells infected with Coxsackie virus B3 (CVB3) at a multiplicity of infection of 5 was extracted at 2 h, 4 h, 6 h and 8 h post-infection to identify differential expression of circSIAE
Quantification of RNA expression by qRTPCR showed that circSIAE expression decreased with CVB3 infection time, and the effect was most obvious at 6 h (Figures 1A, B)

Summary

Introduction

Coxsackievirus B3 (CVB3) is a member of the Picornaviridae family in the genus Enterovirus. It causes viral myocarditis, pancreatitis, and hand, foot and mouth diseases (Li et al, 2015). In CVB3 infection, in particular the virus can induce abnormal expression of several lncRNAs (Tong et al, 2019). Host lncRNA has been shown to affect viral replication and infection; for example, the lncRNA circSIAE Inhibits Replication of CVB3 hypoxia-inducible factor 1-a-antisense 1 has been associated with pro-apoptotic and pro-inflammatory effects in CVB3induced myocarditis through its targeting of miR-138 (Cao et al, 2020). LncRNA AK085865 was shown to promote CVB3 to induce macrophage M2 polarization in patients with viral meningitis by regulating the formation of a complex between interleukin enhancer binding factors 2 and 3 that mediates miR-192 biogenesis (Zhang et al, 2020)

Methods

Results

Conclusion