HSV-1-encoded ICP0 degrades the host deubiquitinase BRCC36 to antagonize interferon antiviral response. (July 2021)

• Record Type: Journal Article
• Authors: Zhang, Liting; Huang, Fan; Liu, Jin; Xu, Ying; Miao, Ying; Yuan, Yukang; Chen, Xiangjie; Zhang, Hong-Guang; Wang, Jun; Zheng, Hui; Zuo, Yibo
• Is Part Of: Molecular immunology. Volume 135(2021)
• Page Start: 28
• Page End: 35
• Publication Date: 2021-07
• Subjects: HSV-1 -- BRCC36 -- Ubiquitination -- Interferon; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2021.03.027
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: HSV-1-encoded ICP0 induces K48-linked polyubiquitination and degradation of BRCC36. 2. HSV-1-encoded ICP0 regulates the host deubiquitinase BRCC36 to inhibit IFN-I antiviral response. 3. HSV-1-induced BRCC36 degradation promotes downmodulation of IFN-I receptor IFNAR1. Abstract: Type I interferon (IFN-I) plays pivotal roles in defense against viral infection. HSV-1 has evolved multiple strategies to evade IFN-I antiviral response. In this study, we revealed a new mechanism that HSV-1-encoded ICP0 regulates the host deubiquitinase BRCC36 to inhibit IFN-I antiviral response. We found that HSV-1 infection rapidly downregulates BRCC36 proteins at the early stage of infection. Further studies demonstrated that HSV-1-encoded ICP0 induces K48-linked polyubiquitination and degradation of BRCC36. Importantly, HSV-1-induced BRCC36 degradation promotes downmodulation of IFN-I receptor IFNAR1, thus restricting host IFN-I antiviral response to facilitate HSV-1 early infection. These findings uncover a novel immune evasion mechanism exploited by HSV-1 and could provide potential strategies for anti-HSV-1 therapy.