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Chicken optineurin suppresses MDA5-mediated interferon β production
Yu Li1, Ning Jiang1, Yaqing Mao2
1Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, P. R. China; Jiangxi Provincial Key laboratory for Animal Science and Technology, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, P. R. China.
Abstract:
Chicken MDA5 (chMDA5), the essential accepted pattern recognition receptors for detecting cytoplasmic viral RNA in chicken, initiates interferon β (IFN-β) generation. However, there is an incomplete elucidation of regulating chMDA5-mediated IFN-β production. NEMO-related protein, optineurin, was identified as inhibitors of virus triggered IFN-β induction in human or mice. In this study, full length of chicken optineurin (chOPTN) was cloned from chicken embryo fibroblast, and its role in inhibiting IFN-β signaling pathway was further explored. Full-length chOPTN encodes 547 amino acids residues and contains unique LC3 interaction region and ubiquitin binding domain. Chicken optineurin mRNA and protein are widely expressed in different tissues, especially the heart, kidney, and bursal fabricius (BF). Overexpressed chOPTN not only inhibits poly I:C or homos-induced human IFN-β promoter activation in 293T cells but also suppresses poly I:C, infectious bursal disease virus (IBDV) genome double-strand RNA (dsRNA), and chMDA5-induced chicken IFN-β (chIFN-β) promoter activation. In addition, we first revealed that chOPTN negatively regulates chIFN-β production via inhibiting ubiquitination of chicken TBK1, which is dependent on the ubiquitin-binding domain of chOPTN. Moreover, chIFN-β stimulus, poly I:C, and IBDV genome dsRNA improve chOPTN expression. Endogenous chOPTN expression is also upregulated by IBDV infection in 293T, DF-1 cells, as well as in BF. Therefore, our results suggested that chOPTN plays an inhibition role of chMDA5-mediated chIFN-β signaling pathway in chicken cells.
Insights
Chicken optineurin (chOPTN) inhibits viral RNA-triggered interferon beta (IFN-β) production by suppressing chicken MDA5 (chMDA5) signaling. This regulation involves inhibiting TBK1 ubiquitination, crucial for chicken antiviral defense.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Chicken MDA5 (chMDA5) is essential for detecting viral RNA and initiating interferon beta (IFN-β) production.
- Optineurin (OPTN) acts as an inhibitor of virus-induced IFN-β in mammals, but its role in chickens is unclear.
Purpose of the Study:
- To clone and characterize chicken optineurin (chOPTN).
- To investigate the role of chOPTN in regulating the chMDA5-mediated IFN-β signaling pathway in chickens.
Main Methods:
- Full-length chOPTN was cloned and its expression analyzed in various chicken tissues.
- Reporter assays were used to assess chOPTN's effect on IFN-β promoter activation induced by poly I:C, dsRNA, and chMDA5.
- The mechanism of inhibition, including TBK1 ubiquitination, was investigated.
Main Results:
- Full-length chOPTN encodes a 547-amino acid protein with LC3 interaction and ubiquitin-binding domains.
- chOPTN is widely expressed in chicken tissues, particularly the heart, kidney, and bursal fabricius (BF).
- Overexpressed chOPTN inhibits poly I:C, dsRNA, and chMDA5-induced IFN-β promoter activation.
- chOPTN negatively regulates chIFN-β production by inhibiting TBK1 ubiquitination, dependent on its ubiquitin-binding domain.
- chOPTN expression is upregulated by IFN-β stimulus, poly I:C, infectious bursal disease virus (IBDV) dsRNA, and IBDV infection.
Conclusions:
- Chicken optineurin (chOPTN) acts as a negative regulator of the chMDA5-mediated IFN-β signaling pathway.
- chOPTN inhibits chIFN-β production by suppressing TBK1 ubiquitination.
- chOPTN expression is induced by viral stimuli, suggesting a feedback mechanism in chicken antiviral immunity.
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