The long non-coding RNA lncRNA-DRNR targets the JMJD6 to enhance replication of infectious bronchitis virus（IBV） by influencing the ISG expression pathway through the JAK-STAT signaling pathway

Abstract

Infectious Bronchitis Virus (IBV) is the causative agent of Infectious Bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Gaining an understanding of the intricate interplay between the virus and its host is crucial for developing novel antiviral strategies. Long non-coding RNA (lncRNA) has emerged as a pivotal regulator of host antiviral immune responses, and our previous studies have indicated that IBV infection disrupts lncRNA stability in host cells, suggesting an unknown regulatory role for lncRNA in IBV pathogenesis. However, it remains unclear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection and demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploration of genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100kb range, we identified JMJD6 as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Moreover, JMJD6 inhibits STAT1 methylation, thereby influencing induction of Interferon-Stimulated Genes (ISGs) through IFN-β-mediated JAK-STAT signaling pathway activation and ultimately promoting intracellular replication of IBV. In summary, our findings unveil the critical role played by lncRNA-DRNR during IBV infection while providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability.