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.

寨卡病毒感染会刺激宿主细胞中的I型干扰素（IFN）反应，从而抑制病毒复制。I型干扰素通过诱导数百种干扰素刺激基因（ISG）的表达发挥抗病毒作用。为了筛选限制Zika病毒复制的抗病毒ISG，我们分别剔除了A549肺癌细胞中的21个ISG，并将PARP12鉴定为Zika病毒复制的强抑制剂。我们的发现表明，PARP12介导了NS1和NS3（参与病毒复制和调节宿主防御反应的非结构性病毒蛋白）的ADP-核糖基化。NS1和NS3的这种修饰触发了它们的蛋白酶体介导的降解。