PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins

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Science Signaling  19 Jun 2018:
Vol. 11, Issue 535, eaas9332
DOI: 10.1126/scisignal.aas9332

Ribosylation restricts infection

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.

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