USP7 Small-molecule Inhibitors Enhance Type I-Interferon Antiviral Efficacy by Destabilizing SOCS1.
In this study, we report that the deubiquitinase USP7 negatively regulates IFN-I-mediated antiviral activity. USP7 physically interacts with SOCS1 and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of JAK-STAT1 signaling. Interestingly, viral infection upregulates USP7 and therefore facilitates viral immune evasion. Importantly, 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.
PMID: 31691271 [PubMed - as supplied by publisher]
Source: Immunology - Category: Allergy & Immunology Authors: Yuan Y, Miao Y, Zeng C, Liu J, Chen X, Qian L, Wang X, Qian F, Yu Z, Wang J, Qian G, Fu Q, Lv H, Zheng H Tags: Immunology Source Type: research