Determination of antiviral action of long non-coding RNA loc107051710 during infectious bursal disease virus infection due to enhancement of interferon production

Xuewei Huang,Yigang Xu,Qingyu Lin,Weilong Guo,Dongfang Zhao,Chunmei Wang,Li Wang,Han Zhou,Yanping Jiang,Wen Cui,Xinyuan Qiao,Yijing Li,Guangpeng Ma,Lijie Tang

doi:10.1080/21505594.2019.1707957

Abstract

ABSTRACT The functions and profiles of lncRNAs during infectious bursal disease virus (IBDV) infection have not been determined, yet. The objectives of this study were to determine the antiviral action of loc107051710 lncRNA during IBDV infection by investigating the relationship between loc107051710 and IRF8, Type I IFN, STATs, and ISGs. DF-1 cells were either left untreated as non-infected controls (n = 1) or infected with IBDV (n = 3). RNA sequencing was applied for analysis of mRNAs and lncRNAs expression. Differentially expressed genes were verified by RT-qPCR. Then identification, of 230 significantly different expressed genes (182 mRNAs and 48 lncRNA) by pairwise comparison of the infected and control groups, was carried out. The functions of differentially expressed lncRNAs were investigated by selection of lncRNAs and mRNAs significantly enriched in the aforementioned biological processes and signaling pathways for construction of lncRNA-mRNA co-expression networks. The techniques of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were applied. It was suggested that these differentially expressed genes were involved in the interaction between the host and IBDV. Loc107051710 was found to have potential antiviral effects. RT-qPCR and western blot were applied and revealed that loc107051710 was required for induction of IRF8, type I IFN, STAT, and ISG expression, and its knockdown promoted IBDV replication. By fluorescence in situ hybridization, it was found that loc107051710 was translocated from the nucleus to the cytoplasm after infection with IBDV. Overall, loc107051710 promoted the production of IFN-α and IFN-β by regulating IRF8, thereby promoting the antiviral activity of ISGs.

Highlights

Infectious bursa disease (IBD) is a highly contagious and immunosuppressive disease that affects young chickens
13 Long noncoding RNAs (lncRNAs) were upregulated, and 35 lncRNAs were downregulated in Infectious bursal disease virus (IBDV)- infected DF-1 cells (Table 7, supplementary materials 2)
We found that the gene ontology (GO) terms were significantly enriched in differentially expressed mRNAs, as well as for just upregulated mRNAs, were mainly involved in biological processes and pathways that may be related to the replication of IBDV, including the type I IFN signaling pathway, defense response to virus, IFN-γmediated signaling pathway, and positive regulation of the type I IFN production signaling pathway (Figure 2 and supplementary materials 3)

Summary

Introduction

Infectious bursa disease (IBD) is a highly contagious and immunosuppressive disease that affects young chickens. It causes high mortality rates and large economic losses to the poultry industry [1,2]. Infectious bursal disease virus (IBDV) mainly causes the destruction of B-lymphocytes in the bursa of Fabricius, which can lead to severe immunosuppression and secondary infections in infected chickens [3,4,5]. The virus (IBDV) is non-enveloped with an icosahedral capsid. The genome of IBDV is bi-segmented, double-stranded RNA [6]

Objectives

Methods

Results

Conclusion