ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP.

Autor: Guo T; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Zuo Y; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Qian L; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Liu J; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Yuan Y; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Xu K; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China., Miao Y; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Feng Q; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Chen X; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Jin L; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Zhang L; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China., Dong C; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. chunshengdong@suda.edu.cn., Xiong S; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. sdxiongfd@126.com.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China. sdxiongfd@126.com., Zheng H; International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. huizheng@suda.edu.cn.; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China. huizheng@suda.edu.cn.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2019 Nov; Vol. 4 (11), pp. 1872-1884. Date of Electronic Publication: 2019 Apr 15.
DOI: 10.1038/s41564-019-0428-3
Abstrakt: Outbreaks of viral infections are a global health burden. Although type I interferon (IFN-I) exerts broad-spectrum antiviral effects, its antiviral efficacy in host cells is largely restricted by viruses. How the antiviral efficacy of IFN-I can be improved remains to be explored. Here, we identified the ADP-ribosyltransferase poly(ADP-ribose) polymerase family member 11 (PARP11) as a potent regulator of IFN-I antiviral efficacy. PARP11 does not restrict IFN-I production induced by vesicular stomatitis virus or Sendai virus but inhibits the strength of IFN-I-activated signalling. Mechanistically, PARP11 mono-ADP-ribosylates the ubiquitin E3 ligase β-transducin repeat-containing protein (β-TrCP). Mono-ADP-ribosylation of β-TrCP promotes IFNα/β receptor subunit 1 (IFNAR1) ubiquitination and degradation. Moreover, PARP11 expression is upregulated by virus infections, including vesicular stomatitis virus, herpes simplex virus-1 and influenza A virus, thus promoting ADP-ribosylation-mediated viral evasion. We further highlight the potential for repurposing clinical ADP-ribosylation inhibitors. We found that rucaparib can target PARP11 to stabilize IFNAR1 and therefore exhibits efficient enhancement of IFN-I signalling and the host antiviral response. Consequently, rucaparib renders mice more resistant to viral infection. Our study updates the understanding of how β-TrCP regulates its substrates and may provide a druggable target for improving IFN antiviral efficacy.
Databáze: MEDLINE
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