| Title: |
Optineurin negatively regulates the induction of IFNβ in response to RNA virus infection |
| Authors: |
Mankouri, J.; Fragkoudis, R.; Richards, K.H.; Wetherill, L.F.; Harris, M.; Kohl, A.; Elliott, R.M.; Macdonald, A. |
| Publisher Information: |
Public Library of Science |
| Publication Year: |
2010 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
The innate immune response provides a critical defense against microbial infections, including viruses. These are recognised by pattern recognition receptors including Toll-like receptors (TLRs) and RIG-I like helicases (RLHs). Detection of virus triggers signalling cascades that induce transcription of type I interferons including IFNβ, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNβ in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNβ induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNβ induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNβ, whereas depletion of optineurin with siRNA promoted virus-induced IFNβ production and decreased RNA virus replication. Immunoprecipitation and immunofluorescence studies identified optineurin in a protein complex containing the antiviral protein kinase TBK1 and the ubiquitin ligase TRAF 3 . Furthermore, mutagenesis studies determined that binding of ubiquitin was essential for both the correct sub-cellular localisation and the inhibitory function of optineurin. This work identifies optineurin as a critical regulator of antiviral signalling and potential target for future antiviral therapy. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.gla.ac.uk/72110/1/72110.pdf; Mankouri, J., Fragkoudis, R., Richards, K.H., Wetherill, L.F., Harris, M., Kohl, A. ORCID logoorcid:0000-0002-1523-9458 , Elliott, R.M. and Macdonald, A. (2010) Optineurin negatively regulates the induction of IFNβ in response to RNA virus infection. PLoS Pathogens , 6(2), e1000778. (doi:10.1371/journal.ppat.1000778 ) |
| DOI: |
10.1371/journal.ppat.1000778 |
| Availability: |
https://eprints.gla.ac.uk/72110/; https://eprints.gla.ac.uk/72110/1/72110.pdf; https://doi.org/10.1371/journal.ppat.1000778 |
| Rights: |
cc_by |
| Accession Number: |
edsbas.89947CCD |
| Database: |
BASE |