Small-molecule inhibitors of ubiquitin-specific protease 7 enhance type-I interferon antiviral efficacy by destabilizing SOCS1.
Immunology
; 159(3): 309-321, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31691271
ABSTRACT
Type-I interferons (IFN-I) are used as common antiviral drugs for a range of viral diseases in clinic. However, the antiviral efficacy of IFN-I is largely restricted by negative regulators of IFN-I signaling in cells. Therefore, identification of intracellular inhibitors of IFN-I signaling is important for developing novel targets to improve IFN-I antiviral therapy. In this study, we report that the deubiquitinase ubiquitin-specific protease 7 (USP7) negatively regulates IFN-I-mediated antiviral activity. USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of Janus kinase-signal transducer and activator of transcription 1 signaling. Interestingly, viral infection up-regulates USP7 and therefore facilitates viral immune evasion. Importantly, the USP7 small-molecule inhibitors P5091 and P22077 inhibit SOCS1 expression and enhance IFN-I antiviral efficacy. Our findings identify a novel regulator of IFN-I antiviral activity and reveal that USP7 inhibitors could be potential enhancement agents for improving IFN-I antiviral therapy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Tiofenos
/
Interferón-alfa
/
Vesiculovirus
/
Inhibidores Enzimáticos
/
Subtipo H1N1 del Virus de la Influenza A
/
Proteína 1 Supresora de la Señalización de Citocinas
/
Peptidasa Específica de Ubiquitina 7
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Immunology
Año:
2020
Tipo del documento:
Article
País de afiliación:
China