Li Zhuowei, Wang Junjun, Wang Siyu, Zhao Wei, Hou Xiaolin, Wang Jianfang, Dong Hong, Zhou Shuanghai, Gao Yuan, Yao Wei, Li Huanrong, Liu Xuewei
College of Animal Science and Technology, Beijing University of Agriculture, Beijing, China.
Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing Traditional Chinese Veterinary Engineering Center, Beijing University of Agriculture, Beijing, China.
Front Microbiol. 2024 Jun 19;15:1417404. doi: 10.3389/fmicb.2024.1417404. eCollection 2024.
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.
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.
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.
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.
猪繁殖与呼吸综合征病毒（PRRSV）给全球养猪业造成了巨大经济损失。目前的疫苗选择对PRRSV传播的保护有限，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全球PRRSV的传播。
在本研究中，我们合成了一种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。该聚合物以天然药物DIC和GQDs为原料，通过静电吸附法合成。
我们的研究结果表明，DIC通过抑制PRRSV复制阶段表现出高抗PRRSV活性。转录组测序分析显示，DIC处理可刺激与Janus激酶/信号转导子和转录激活子（JAK/STAT）信号通路相关的基因。在猪肺泡巨噬细胞（PAM）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）上调。动物攻毒实验进一步证实，DIC-GQDs有效减轻了PRRSV感染猪肺部、脾脏和淋巴结的临床症状和病理反应。
这些发现表明，DIC-GQDs通过激活JAK/STAT信号通路显著抑制PRRSV增殖。因此，DIC-GQDs有望成为PRRSV感染的替代治疗方法。
