Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
J Virol. 2019 May 1;93(10). doi: 10.1128/JVI.00001-19. Print 2019 May 15.
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting many swine-producing regions. Current vaccination strategies and antiviral drugs provide only limited protection. PRRSV infection can cleave mitochondrial antiviral signaling protein (MAVS) and inhibit the induction of type I interferon. The antiviral effector molecules that are involved in host protective responses to PRRSV infection are not fully understood. Here, by using transcriptome sequencing, we found that a zinc finger antiviral protein, ZAP, is upregulated in MAVS-transfected Marc-145 cells and that ZAP suppresses PRRSV infection at the early stage of replication. We also found that the viral protein Nsp9, an RNA-dependent RNA polymerase (RdRp), interacts with ZAP. The interacting locations were mapped to the zinc finger domain of ZAP and N-terminal amino acids 150 to 160 of Nsp9. These findings suggest that ZAP is an effective antiviral factor for suppressing PRRSV infection, and they shed light on virus-host interaction. PRRSV continues to adversely impact the global swine industry. It is important to understand the various antiviral factors against PRRSV infection. Here, a zinc finger protein, termed ZAP, was screened from MAVS-induced antiviral genes by transcriptome sequencing, and it was found to remarkably suppress PRRSV replication and interact with PRRSV Nsp9. The zinc finger domain of ZAP and amino acids 150 to 160 of Nsp9 are responsible for the interaction. These findings expand the antiviral spectrum of ZAP and provide a better understanding of ZAP antiviral mechanisms, as well as virus-host interactions.
猪繁殖与呼吸综合征病毒（PRRSV）是影响许多养猪地区的最重要的经济病原体之一。目前的疫苗接种策略和抗病毒药物仅提供有限的保护。PRRSV 感染可以切割线粒体抗病毒信号蛋白（MAVS）并抑制 I 型干扰素的诱导。参与宿主对 PRRSV 感染的保护性反应的抗病毒效应分子尚未完全了解。在这里，我们通过使用转录组测序发现，锌指抗病毒蛋白 ZAP 在 MAVS 转染的 Marc-145 细胞中上调，并且 ZAP 抑制 PRRSV 感染在复制的早期阶段。我们还发现病毒蛋白 Nsp9，一种 RNA 依赖性 RNA 聚合酶（RdRp），与 ZAP 相互作用。相互作用的位置被映射到 ZAP 的锌指结构域和 Nsp9 的 N 端氨基酸 150 到 160。这些发现表明 ZAP 是抑制 PRRSV 感染的有效抗病毒因子，并为病毒-宿主相互作用提供了线索。PRRSV 继续对全球养猪业产生不利影响。了解针对 PRRSV 感染的各种抗病毒因素非常重要。在这里，通过转录组测序从 MAVS 诱导的抗病毒基因中筛选出一种锌指蛋白，称为 ZAP，它显著抑制 PRRSV 复制并与 PRRSV Nsp9 相互作用。ZAP 的锌指结构域和 Nsp9 的氨基酸 150 到 160 负责相互作用。这些发现扩展了 ZAP 的抗病毒谱，并更好地理解了 ZAP 的抗病毒机制以及病毒-宿主相互作用。
