The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity.
Virol J
; 11: 209, 2014 Dec 07.
Article
en En
| MEDLINE
| ID: mdl-25481026
ABSTRACT
BACKGROUND:
The outcome of a viral infection is regulated by complex interactions of viral and host factors. SARS coronavirus (SARS-CoV) engages and regulates several innate immune response pathways during infection. We have previously shown that the SARS-CoV Papain-like Protease (PLpro) inhibits type I interferon (IFN) by inhibiting IRF3 phosphorylation thereby blocking downstream Interferon induction. This finding prompted us to identify other potential mechanisms of inhibition of PLpro on IFN induction.METHODS:
We have used plasmids expressing PLpro and IRF3 including an IRF3 mutant that is constitutively active, called IRF3(5D). In these experiments we utilize transfections, chromatin immunoprecipitation, Electro-mobility Shift Assays (EMSA) and protein localization to identify where IRF3 and IRF3(5D) are inhibited by PLpro.RESULTS:
Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro's DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response.CONCLUSION:
These results demonstrate an additional mechanism that PLpro is able to inhibit IRF3 signaling. These data suggest novel innate immune antagonism activities of PLpro that may contribute to SARS-CoV pathogenesis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas Virales
/
Cisteína Endopeptidasas
/
Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo
/
Factor 3 Regulador del Interferón
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Virol J
Asunto de la revista:
VIROLOGIA
Año:
2014
Tipo del documento:
Article