Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, China.
Virus Res. 2023 Sep;334:199159. doi: 10.1016/j.virusres.2023.199159. Epub 2023 Jun 30.
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.
非洲猪瘟病毒（ASFV）是非洲猪瘟（ASF）的病原体，由于其在国内猪中的死亡率接近 100%，对养猪业造成了极大的危害，是最具危害性的猪病之一。自 ASF 首次报告以来，科学家们一直在努力开发抗 ASF 疫苗；然而，目前尚无临床有效的 ASF 疫苗。因此，开发预防 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）对 ASFV 的抗病毒活性，TF 是一种主要从红茶中分离得到的天然化合物。我们发现 TF 在原代猪肺泡巨噬细胞（PAMs）中以非细胞毒性浓度在体外强烈抑制 ASFV 的复制。从机制上讲，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来抑制 ASFV 的复制。此外，我们发现 TF 上调了 ASFV 感染和未感染细胞中的 AMPK（5'-AMP 激活蛋白激酶）信号通路，并且 AMPK 激动剂 MK8722 以剂量依赖的方式上调 AMPK 信号通路并抑制 ASFV 增殖。值得注意的是，TF 对 AMPK 激活和 ASFV 抑制的作用部分被 AMPK 抑制剂 dorsomorphin 逆转。此外，我们发现 TF 下调了与脂质合成相关的基因的表达，并降低了 ASFV 感染细胞中总胆固醇和总甘油三酯的细胞内积累，表明 TF 可能通过破坏脂质代谢来抑制 ASFV 的复制。总之，我们的研究结果表明，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。
