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Abstract：
African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), which is one of the most harmful swine diseases in the pig industry because of its nearly 100% mortality rate in domestic pigs and results in incalculable economic loss. Ever since ASF was initially reported, scientists have worked to develop anti-ASF vaccines; however, currently no clinically effective vaccine for ASF is available. Therefore, the development of novel measures to prevent ASFV infection and transmission is essential. In this study, we aimed to investigate the anti-ASF activity of theaflavin (TF), a natural compound mainly isolated from black tea. We found that TF potently inhibited ASFV replication at non-cytotoxic concentrations ex vivo in primary porcine alveolar macrophages (PAMs). Mechanistically, we found that TF inhibited ASFV replication by acting on cells rather than interacting directly with ASFV to inhibit viral replication. Further, we found that TF upregulated the AMPK (5\'-AMP-activated protein kinase) signaling pathway in ASFV-infected and uninfected cells, and treatment with the AMPK agonist MK8722 upregulated the AMPK signaling pathway and inhibited ASFV proliferation in a dose-dependent manner. Notably, the effects of TF on AMPK activation and ASFV inhibition were partially reversed by the AMPK inhibitor dorsomorphin. In addition, we found that TF down-regulated the expression of genes related to lipid synthesis and decreased the intracellular accumulation of total cholesterol and total triglycerides in ASFV-infected cells, suggesting that TF may inhibit ASFV replication by disrupting lipid metabolism. In summary, our results demonstrated that TF is an ASFV infection inhibitor and revealed the mechanism by which ASFV replication is inhibited, providing a novel mechanism and potential lead compound for the development of anti-ASFV drugs.
摘要：
非洲猪瘟病毒(ASFV)是非洲猪瘟(ASF)的病原,这是养猪业中最有害的猪病之一，因为它在家猪中的死亡率接近100%，并造成无法估量的经济损失。自从ASF最初被报道以来，科学家一直致力于开发抗ASF疫苗；然而，目前尚无临床上有效的ASF疫苗。因此,制定预防ASFV感染和传播的新措施至关重要。在这项研究中,我们旨在研究茶黄素（TF）的抗ASF活性，一种主要从红茶中分离出来的天然化合物。我们发现TF在原代猪肺泡巨噬细胞（PAMs）中在非细胞毒性浓度下有效抑制ASFV复制。机械上,我们发现TF通过作用于细胞而不是直接与ASFV相互作用来抑制病毒复制,从而抑制ASFV复制.Further,我们发现TF在ASFV感染和未感染的细胞中上调AMPK（5'-AMP激活的蛋白激酶）信号通路，和用AMPK激动剂MK8722治疗上调AMPK信号传导途径并以剂量依赖性方式抑制ASFV增殖。值得注意的是,TF对AMPK激活和ASFV抑制的影响被AMPK抑制剂dorsomorphin部分逆转。此外,我们发现TF下调与脂质合成相关的基因的表达，并降低ASFV感染细胞中总胆固醇和总甘油三酯的细胞内积累，提示TF可能通过破坏脂质代谢来抑制ASFV的复制。总之,我们的结果表明，TF是一种ASFV感染抑制剂，并揭示了抑制ASFV复制的机制，为开发抗ASFV药物提供了新的机制和潜在的先导化合物。
