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Review
. 2018 Apr 26:9:853.
doi: 10.3389/fimmu.2018.00853. eCollection 2018.

The Role of Optineurin in Antiviral Type I Interferon Production

Ahmed Outlioua  1   2   3 , Marie Pourcelot  1   2   4 , Damien Arnoult  1   2
Affiliations
Review

The Role of Optineurin in Antiviral Type I Interferon Production

Ahmed Outlioua et al. Front Immunol. .

Abstract

After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity. This review summarizes the sensing of viruses and the signaling leading to type I IFN production following TBK1 activation through its ubiquitination and the sensing of ubiquitin chains by OPTN at the Golgi apparatus.

Keywords: Golgi apparatus; TBK1; innate immunity; optineurin; viruses.

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Figures

Figure 1
Figure 1
The RIG-I-like receptors and toll-like receptor (TLR) 3 signaling pathway. After a viral infection, double-strand RNA (dsRNA) in the cytosol is sensed by RIG-I while it is sensed by TLR3 in the endosomes. Through the adaptors MAVS and TRIF, respectively, some E3 ubiquitin ligases TRAFs are recruited and polyubiquitinated. On the K63-linked ubiquitin chains, on the one hand, the IKK complex is activated leading to NF-κB activation and the production of pro-inflammatory cytokines and on the other hand, the IKK-related kinase TBK1 is activated triggering the phosphorylation of IRF3 and IFR7 for the production of type I IFNs.
Figure 2
Figure 2
The involvement of optineurin (OPTN) in TBK1 activation following RIG-I-like receptors or toll-like receptor (TLR) 3 stimulation. After infection, viral double-strand RNAs (dsRNAs) are sensed by RIG-I in the cytosol or TLR3 in the endosomes. The corresponding adaptors, MAVS and TRIF, trigger the formation of specific signalosomes leading to the ubiquitination of TBK1. At the Golgi apparatus, OPTN recruits ubiquitinated TBK1 via its ubiquitin-binding domain, leading to the trans-autophosphorylation of this kinase. Activated TBK1 then phosphorylates IRF3, leading to the production of type I interferons (IFNs). TBK1 may directly interact with the N-terminus part of OPTN and promotes its phosphorylation. The function of the phosphorylation of TBK1 remains to be determined.
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