Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. Type I interferon response to ZIKV infection in host cells suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs). The study aims to demonstrate the anti-ZIKV mechanism of PARP11. PARP11 knock out and overexpressing A549 cell lines were constructed to evaluate the anti-ZIKV function of PARP11. PARP11−/−, PARP12−/− and PARP11−/−PARP12−/− HEK293T cell lines were constructed to explain the synergistic effect of PARP11 and PARP12 on NS1 and NS3 protein degradation. Western blotting, immunofluorescence and immunoprecipitation assay were performed to illustrate the interaction between PARP11 and PARP12. Both mRNA and protein levels of PARP11 were induced in WT but not IFNAR1−/− cells in response to IFNα or IFNβ stimulation and ZIKV infection. ZIKV replication was suppressed in cells expressed PARP11 but was enhanced in PARP11−/− cells. PARP11 suppressed ZIKV independently on itself PARP enzyme activity. PARP11 interacted with PARP12 and promoted PARP12-mediated ZIKV NS1 and NS3 protein degradation. We identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that it cooperated with PARP12 to enhance ZIKV NS1 and NS3 protein degradation. Our findings have broadened the understanding of the anti-viral function of ADP-ribosyltransferase family members, and provided potential therapeutic targets against viral ZIKV infection.

中文翻译：

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ADP-核糖基转移酶 PARP11 与 PARP12 协同抑制寨卡病毒

寨卡病毒 (ZIKV) 感染和 ZIKV 流行病一直在世界各地无声无息地蔓延，其相关的小头畸形和其他严重的先天性神经系统并发症对全球公共卫生构成重大威胁。I 型干扰素对宿主细胞中 ZIKV 感染的反应通过诱导干扰素刺激基因 (ISG) 的表达来抑制病毒复制。该研究旨在证明 PARP11 的抗 ZIKV 机制。构建PARP11敲除和过表达A549细胞系以评估PARP11的抗ZIKV功能。构建 PARP11-/-、PARP12-/- 和 PARP11-/-PARP12-/- HEK293T 细胞系以解释 PARP11 和 PARP12 对 NS1 和 NS3 蛋白降解的协同作用。蛋白质印迹法，进行免疫荧光和免疫沉淀测定以说明 PARP11 和 PARP12 之间的相互作用。响应于 IFNα 或 IFNβ 刺激和 ZIKV 感染，PARP11 的 mRNA 和蛋白质水平在 WT 但不是 IFNAR1-/- 细胞中被诱导。ZIKV 复制在表达 PARP11 的细胞中受到抑制，但在 PARP11-/- 细胞中增强。PARP11 独立于自身 PARP 酶活性抑制 ZIKV。PARP11 与 PARP12 相互作用并促进 PARP12 介导的 ZIKV NS1 和 NS3 蛋白降解。我们将 ADP-核糖基转移酶 PARP11 鉴定为抗 ZIKV ISG，并发现它与 PARP12 合作以增强 ZIKV NS1 和 NS3 蛋白降解。我们的研究结果拓宽了对 ADP-核糖基转移酶家族成员抗病毒功能的理解，