RT Journal Article SR Electronic T1 PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins JF Science Signaling JO Sci. Signal. FD American Association for the Advancement of Science SP eaas9332 DO 10.1126/scisignal.aas9332 VO 11 IS 535 A1 Li, Lili A1 Zhao, Hui A1 Liu, Ping A1 Li, Chunfeng A1 Quanquin, Natalie A1 Ji, Xue A1 Sun, Nina A1 Du, Peishuang A1 Qin, Cheng-Feng A1 Lu, Ning A1 Cheng, Genhong YR 2018 UL http://stke.sciencemag.org/content/11/535/eaas9332.abstract AB Type I interferon signaling drives the expression of hundreds of interferon-stimulated genes (ISGs) that are critical for host and cellular defense against viral infection. To identify ISGs that limit Zika virus infection, Li et al. screened CRISPR knockout cell lines and found that loss of PARP12 increased viral replication. Truncation and pharmacological inhibition of PARP12 indicated that antiviral activity required the PARP domain–dependent ADP-ribosylation of required viral proteins, which led to their ubiquitylation and degradation. This work identifies a distinct antiviral mechanism and suggests that PARP agonists may have clinical utility if repurposed as treatments for Zika virus.Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus.