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Publication from Hui ZHENG lab, Nature Microbiology

  

  

On April 15th, 2019, researchers at Dr.Zheng’s, Dr.Xiong’s and Dr. Dong’s groups published an article entitled “ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADPribosylating the ubiquitin E3 ligase β-TrCP” in Nature Microbiology.

  

  

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. The researchers 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. The researchers further highlight the potential for repurposing clinical ADP-ribosylation inhibitors. They 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. This study updates the understanding of how β-TrCP regulates its substrates and may provide a druggable target for improving IFN antiviral efficacy.

  

  

Guo Tingting is the first author. Zuo Yibo, Qian Liping, Liu Jin etc. are contributing authors. Prof. Zheng Hui, Prof. Xiong Sidong and Prof. Dong Chunsheng are the corresponding author. This work was supported by the National Natural Science Foundation of China (31570865, 3160069531501139), and the Program of 1000 Young Talents (2014).