关键词: JAK/STAT signaling pathway PRRSV antiviral dicoumarol graphene oxide quantum dot polymer

来  源:   DOI:10.3389/fmicb.2024.1417404   PDF(Pubmed)

Abstract:
UNASSIGNED: Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses in the global swine industry. The current vaccine options offer limited protection against PRRSV transmission, and there are no effective commercial antivirals available. Therefore, there is an urgent need to develop new antiviral strategies that slow global PRRSV transmission.
UNASSIGNED: In this study, we synthesized a dicoumarol-graphene oxide quantum dot (DIC-GQD) polymer with excellent biocompatibility. This polymer was synthesized via an electrostatic adsorption method using the natural drug DIC and GQDs as raw materials.
UNASSIGNED: Our findings demonstrated that DIC exhibits high anti-PRRSV activity by inhibiting the PRRSV replication stage. The transcriptome sequencing analysis revealed that DIC treatment stimulates genes associated with the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway. In porcine alveolar macrophages (PAMs), DIC-GQDs induce TYK2, JAK1, STAT1, and STAT2 phosphorylation, leading to the upregulation of JAK1, STAT1, STAT2, interferon-β (IFN-β) and interferon-stimulated genes (ISGs). Animal challenge experiments further confirmed that DIC-GQDs effectively alleviated clinical symptoms and pathological reactions in the lungs, spleen, and lymph nodes of PRRSV-infected pigs.
UNASSIGNED: These findings suggest that DIC-GQDs significantly inhibits PRRSV proliferation by activating the JAK/STAT signalling pathway. Therefore, DIC-GQDs hold promise as an alternative treatment for PRRSV infection.
摘要:
猪繁殖与呼吸综合征病毒(PRRSV)在全球养猪业造成了巨大的经济损失。目前的疫苗选择对PRRSV传播提供了有限的保护,并且没有有效的商业抗病毒药物。因此,迫切需要开发新的抗病毒策略来减缓PRRSV在全球的传播.
在这项研究中,我们合成了具有优异生物相容性的双香豆素-氧化石墨烯量子点(DIC-GQD)聚合物。该聚合物是以天然药物DIC和GQDs为原料,通过静电吸附法合成的。
我们的发现证明DIC通过抑制PRRSV复制阶段表现出高的抗PRRSV活性。转录组测序分析揭示DIC处理刺激与Janus激酶/信号转导子和转录激活因子(JAK/STAT)信号通路相关的基因。在猪肺泡巨噬细胞(PAMs)中,DIC-GQDs诱导TYK2、JAK1、STAT1和STAT2磷酸化,导致JAK1,STAT1,STAT2,干扰素-β(IFN-β)和干扰素刺激基因(ISG)的上调。动物激发实验进一步证实DIC-GQDs能有效缓解肺部临床症状和病理反应,脾,脾和PRRSV感染猪的淋巴结。
这些发现表明DIC-GQD通过激活JAK/STAT信号通路显著抑制PRRSV增殖。因此,DIC-GQD有望作为PRRSV感染的替代疗法。
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