Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines.

Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines.
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Platycodin D 抑制原代细胞系和已建立细胞系中的 2 型猪繁殖与呼吸综合征病毒

DOI:
10.3390/v10110657
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发表时间:
2018-11-21
期刊:
Viruses
影响因子:
--
通讯作者:
Chen J
Chen J
中科院分区:
其他
文献类型:
--
作者:
Zhang M;Du T;Long F;Yang X;Sun Y;Duan M;Zhang G;Liu Y;Zhou EM;Chen W;Chen J

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猪繁殖与呼吸综合征病毒(Porcine reproductive and respiratory syndrome virus,PRRSV)是一种严重威胁养猪业的病毒。目前,疫苗接种策略对PRRSV传播提供的保护非常有限。因此,迫切需要开发新的抗病毒策略。桔梗皂苷D(Platycodin D,PD)是从桔梗(Platycodon grandiflorum)中提取的一种具有生物活性的三萜皂苷类化合物,是一种治疗肺部疾病和呼吸系统疾病的传统中药。在这里,我们证明PD在Marc-145细胞和原代猪肺泡巨噬细胞中对PRRSV感染表现出有效的活性。PD对高致病性2型PRRSVGD-HD株、GD-XH株以及经典的CH-1a株和VR 2332株均表现出广谱的体外抑制活性。1-4 μM浓度的PD以剂量依赖性方式显著抑制PRRSV RNA合成、病毒蛋白表达和子代病毒产生。在Marc-145细胞中,PD对四种测试的PRRSV毒株感染的EC 50值范围为0.74至1.76 μM。从机制上讲,PD通过直接与病毒体相互作用抑制PRRSV复制,因此影响病毒生命周期的多个阶段,包括病毒进入和子代病毒释放。此外,PD降低了PAM中PRRSV和LPS诱导的细胞因子(IFN-α、IFN-β、IL-1α、IL-6、IL-8和TNF-α)的产生。总之,我们的研究结果表明,PD是一个有效的抑制剂PPRSV感染在体外。然而,进一步的体内研究是必要的,以确认PD作为一种潜在的新型和有效的PPRSV抑制剂在猪。
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1–4 μM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 μM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-β, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.
缺乏CD163的猪富含清道夫受体的富含半胱氨酸的结构域5具有对猪生殖和呼吸综合征病毒1感染的抗性。
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