| First Author | Guo T | Year | 2019 |
| Journal | Nat Microbiol | Volume | 4 |
| Issue | 11 | Pages | 1872-1884 |
| PubMed ID | 30988430 | Mgi Jnum | J:298222 |
| Mgi Id | MGI:6477456 | Doi | 10.1038/s41564-019-0428-3 |
| Citation | Guo T, et al. (2019) ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase beta-TrCP. Nat Microbiol 4(11):1872-1884 |
| abstractText | 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 beta-transducin repeat-containing protein (beta-TrCP). Mono-ADP-ribosylation of beta-TrCP promotes IFNalpha/beta 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 beta-TrCP regulates its substrates and may provide a druggable target for improving IFN antiviral efficacy. |
