RT Journal Article
SR Electronic
T1 <em>PARP12</em> 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.