The long noncoding RNA loc107053557 acts as a gga-miR-3530-5p sponge to suppress the replication of vvIBDV through regulating STAT1 expression

ABSTRACT

Infectious bursal disease virus (IBDV) causes immunosuppression and high mortality in young chickens. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are important regulators during viral infection. However, detailed the regulatory mechanisms of lncRNA-miRNA-mRNA have not yet been described in IBDV infection. Here, we analysed the role of lncRNA53557/gga-miR-3530-5p/STAT1 axis in very virulent IBDV (vvIBDV) infection. Evidently upregulated expression of lncRNA53557 was observed in bursa of Fabricius and DT40 cells. Meanwhile, overexpression of lncRNA53557 promoted STAT1 expression and inhibited vvIBDV replication and vice versa, indicating that the upregulation of lncRNA53557 was part of the host antiviral defence. The subcellular fractionation assay confirmed that lncRNA53557 can be localized in the cytoplasm. Further, dual-luciferase reporter, RNA pulldown, FISH and RT-qPCR assays revealed that lncRNA53557 were directly bound to gga-miR-3530-5p and had a negative regulatory relationship between them. Subsequent mechanistic analysis showed that lncRNA53557 acted as a competing endogenous RNA (ceRNA) of gga-miR-3530-5p to relieve the repressive effect of gga-miR-3530-5p on its target STAT1, as well as Mx1, OASL, and ISG15, thereby suppressing vvIBDV replication. The study reveals that a network of enriched lncRNAs and lncRNA-associated ceRNA is involved in the regulation of IBDV infection, offering new insight into the mechanisms underlying IBDV-host interaction.

KEYWORDS:

• Infectious bursal disease virus
• bursa of fabricius
• lncRNA53557
• gga-miR-3530-5p
• STAT1
• interferon-stimulated genes

Acknowledgements

We thank Novel Bioinformatics Ltd., Co for the support of bioinformatics analysis and we also thank GENE DENOVO for the support of uploading the sequencing data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

XWH and XNW designed the experiments. XWH, ZFS, and LW performed the experiment, XWH, YPJ, WC, and XYQ analysed the data. XWH, YJL, HZ, and LJT drafted and revised the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Animal experiments were carried out in accordance with the recommendations in the institutional and national guidelines for animal care and use. The protocol was approved by the Committee on the Ethics of Animal Experiments of Northeast Agricultural University, Harbin, China (2016NEFU–315, 13 April 2017).

Data Availability statement

The raw data presented in this study can be found in the NCBI short reads archive and accession number is PRJNA635782. For information linking please refer to: https://www.ncbi.nlm.nih.gov/search/all/?term=PRJNA635782.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2333237.

Additional information

Funding

This work is supported by the National Key Research and Development Program of China [Grant number 2022YFD1800304] and the Natural Science Foundation of Shandong Province [Grant number ZR2022QC116].