LiCl inhibits PRRSV infection by enhancing Wnt/β-catenin pathway and suppressing inflammatory responses
LiCl inhibits PRRSV infection by enhancing Wnt/β-catenin pathway and suppressing inflammatory responses
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DOI：
10.1016/j.antiviral.2015.02.010
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发表时间：
2015-05-01
影响因子：
7.6
通讯作者：
Mao, Xiang
中科院分区：
文献类型：
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作者：
Hao, Hong-ping;Wen, Li-bin;Mao, Xiang
氯化锂（LiCl）已被用作躁狂抑郁症治疗中的情绪稳定剂。最近的研究表明，LiCl也是一些DNA和RNA病毒的有效抑制剂。猪繁殖与呼吸综合征病毒（Porcine reproductive and respiratory syndrome virus，PRRSV）是现代养猪业的重要病毒性病原。本研究采用空斑形成试验、Q-PCR和Western blot分析方法，研究了氯化锂对猪繁殖与呼吸综合征病毒（PRRSV）感染的抑制作用。结果表明，LiCl对MARC-145和PAM-CD 163细胞的PRRSV感染有抑制作用。先前的报道表明，LiCl可以在不存在Wnt配体的情况下诱导Wnt途径。在我们的研究中，我们证明了LiCl激活PRRSV感染细胞中的Wnt途径。此外，β-catenin的敲低或Wnt/β-catenin通路抑制剂PNU 74654的敲低均能逆转LiCl的抗病毒作用，提示LiCl对PRRSV复制的抑制作用可能与Wnt/β-catenin通路的激活有关。我们还发现LiCl处理后较低的病毒复制与促炎性IL-8、IL-6、IL-1 β、肿瘤坏死因子α的mRNA水平降低和NE-κ B核转位减少有关。总的来说，我们的数据表明，氯化锂抑制PRRSV感染通过增强Wnt/β-连环蛋白途径和抑制促炎反应。(C)2015 Elsevier B. V.版权所有。
Lithium chloride (LiCl) has been used as a mood stabilizer in the manic depressive disorders treatment. Recent studies show that LiCl is also a potent inhibitor for some DNA and RNA viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is an important viral pathogen in modern pig industry. In this study, we assessed the inhibitory effect of LiCl on PRRSV infection using plque-formation assay, Q-PCR and Western blot analysis. Our results showed that LiCl could inhibit PRRSV infection in MARC-145 and PAM-CD163 cells. Previous reports have shown that LiCl could induce the Wnt pathway in the absence of Wnt ligands. In our studies, we demonstrated that LiCl activates the Wnt pathway in PRRSV infected cells. Additionally, the knockdown of beta-catenin or the Wnt/beta-catenin pathway inhibitor PNU74654 was able to reverse the antiviral effect of LiCl, which suggested that the inhibitory effect of LiCl against PRRSV replication might be associated with the activation of the Wnt/beta-catenin pathway. We also found that lower viral replication after LiCl treatment was associated with the reduced mRNA levels of pro-inflammatory IL-8, IL-6, IL-1 beta, tumor necrosis factor a and decreased NE-kappa B nuclear translocation. Collectively, our data demonstrated that LiCl inhibited PRRSV infection by enhancing Wnt/beta-catenin pathway and suppressing pro-inflammatory responses. (C) 2015 Elsevier B.V. All rights reserved.