Optineurin negatively regulates the induction of IFNbeta in response to RNA virus infection.
PLoS Pathog
; 6(2): e1000778, 2010 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-20174559
ABSTRACT
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 IFNbeta, which are pivotal for the initiation of an anti-viral state. Despite the essential role of IFNbeta in the anti-viral response, there is an incomplete understanding of the negative regulation of IFNbeta induction. Here we provide evidence that expression of the Nemo-related protein, optineurin (NRP/FIP2), has a role in the inhibition of virus-triggered IFNbeta induction. Over-expression of optineurin inhibited Sendai-virus (SeV) and dsRNA triggered induction of IFNbeta, whereas depletion of optineurin with siRNA promoted virus-induced IFNbeta 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 TRAF3. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por Respirovirus
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Transdução de Sinais
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Regulação Viral da Expressão Gênica
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Interferon beta
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Fator de Transcrição TFIIIA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido