Pyrithione inhibits porcine reproductive and respiratory syndrome virus replication through interfering with NF-KB and heparanase
Pyrithione inhibits porcine reproductive and respiratory syndrome virus replication through interfering with NF-KB and heparanase
复制标题
吡啶硫酮通过干扰 NF-kB 和乙酰肝素酶抑制猪繁殖与呼吸综合征病毒复制
DOI：
10.1016/j.vetmic.2017.01.033
复制
发表时间：
2017-03-01
影响因子：
3.3
通讯作者：
Liu, Xiaohong
中科院分区：
文献类型：
--
作者：
Guo, Chunhe;Zhu, Zhenbang;Liu, Xiaohong
猪繁殖与呼吸综合征病毒（PRRSV）对养猪业持续构成威胁，在全球范围内造成巨大经济损失。目前的疫苗接种策略只能提供有限的针对 PRRSV 感染的保护。因此，需要开发新的抗病毒策略。吡啶硫酮 (PT) 是一种锌离子载体，被用作抗菌和抗真菌剂，有证据表明 PT 可以抑制各种 RNA 病毒的复制。然而，迄今为止还没有关于其对抗 PRRSV 感染的效果的数据。在这项研究中，我们发现 PT 强烈抑制 Marc-145 细胞中 PRRSV 的复制。在猪肺泡巨噬细胞中也发现了类似的抑制作用，猪肺泡巨噬细胞是猪体内 PRRSV 感染的主要靶细胞类型。 PT 还可以减弱感染后期病毒诱导的细胞凋亡。此外，我们提供的证据表明，PT 导致细胞外锌离子快速输入细胞内，而输入的 Zn' 是其抗病毒特性的原因。我们研究了 PT 抗 PRRSV 的分子机制，发现 PT 抑制 NF-KB 和乙酰肝素酶，产生硫酸乙酰肝素表达增加，阻止病毒和细胞因子的释放，从而减少病毒复制。这些发现表明 PT 有潜力开发针对 PRRSV 感染的预防和治疗策略。 (C)2017 Elsevier B.V. 保留所有权利。
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pig industry, causing high economic losses worldwide. Current vaccination strategies provide only limited protection against PRRSV infection. Consequently, there is a need to develop new antiviral strategies. Pyrithione (PT), a zinc ionophore, is used as an antibacterial and antifungal agent, and evidence has shown that PT inhibits the replication of various RNA viruses. However, there is no data regarding its effects against PRRSV infection until now. In this study, we showed that PT strongly inhibited PRRSV replication in Marc-145 cells. Similar inhibitory effects were also found in porcine alveolar macrophages, the major target cell type of PRRSV infection in pigs in vivo. PT also attenuated virus-induced apoptosis during the late phase of infection. In addition, we provided evidence that PT caused a rapid import of extracellular zinc ions into cells, and imported Zn' was responsible for its antiviral property. We investigated the molecular mechanisms of PT against PRRSV and found that PT inhibited NF-KB and heparanase, producing the increased heparan sulfate expression to block the release of virus and cytokines, thus decreasing viral replication. These findings suggest that PT has the potential to the development of prophylactic and therapeutic strategies against PRRSV infection. (C)2017 Elsevier B.V. All rights reserved.