Up-regulated lncRNA-TLR3 inhibits infectious bursal disease virus replication by promoting TLR3 expression to enhance TRIF-IRF7 mediated type-I IFN production
Description
Infectious bursal disease virus (IBDV) is a highly contagious and immunosuppressive avian pathogen that causes severe economic losses to the global poultry industry. However, the molecular mechanisms underlying IBDV–host innate immune interactions remain incompletely defined. In this study, we identified an IBDV-responsive long non-coding RNA, termed lncRNA-TLR3, and its associated target gene Toll-like receptor 3 (TLR3), and systematically investigated their roles in antiviral innate immunity. We demonstrated that IBDV infection markedly upregulated TLR3 expression and activated the TRIF–IRF7 signaling cascade, leading to robust induction of type I interferons (IFN-α/β) and interferon-stimulated genes (ISGs), thereby restricting viral replication. Bioinformatic analyses and RNA fluorescence in situ hybridization (RNA-FISH) confirmed that lncRNA-TLR3 lacks protein-coding potential and is predominantly localized in the cytoplasm. Notably, lncRNA-TLR3 expression was significantly induced by IBDV infection both in vitro and in vivo. Gain- and loss-of-function assays revealed that lncRNA-TLR3 positively regulated TLR3 expression, enhanced TRIF–IRF7–mediated IFN-I and ISGs responses, and consequently suppressed IBDV replication. Rescue experiments further demonstrated that the antiviral activity of lncRNA-TLR3 is largely dependent on TLR3 signaling. Moreover, RNA-FISH assays revealed cytoplasmic colocalization of lncRNA-TLR3 and TLR3 in IBDV-infected cells and bursal tissues. Collectively, our findings identify lncRNA-TLR3 as a positive regulator of TLR3-mediated innate immunity and provide new mechanistic insights into host–IBDV interactions, highlighting lncRNA-TLR3 as a potential antiviral target in poultry.
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Institutions
- Qingdao Agricultural University
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Funders
- Natural Science Foundation of Shandong ProvinceGrant ID: ZR2022QC116