The role of optineurin in antiviral type I interferon production

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. After a viral infection, the innate immune response is the first line of defense. Replication of a virus into host cells engenders molecular marks that are called pathogen-associated molecular patterns (PAMPs). The presence of PAMPs like viral nucleic acids is sensed by germline-encoded pattern-recognition receptors (PRRs) that generate a series of signaling pathways conducting to the prompt production of pro-inflammatory cytokines and type-I interferons (IFNs) (IFNa/IFNβ) (1, 2) to establish the antiviral immune response.