State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou, China.
J Virol. 2023 Aug 31;97(8):e0058623. doi: 10.1128/jvi.00586-23. Epub 2023 Aug 15.
African swine fever (ASF) is a devastating disease caused by the African swine fever virus (ASFV) that adversely affects the pig industry. The spleen is the main target organ of ASFV; however, the function of metabolites in the spleen during ASFV infection is yet to be investigated. To define the metabolic changes in the spleen after ASFV infection, untargeted and targeted metabolomics analyses of spleens from ASFV-infected pigs were conducted. Untargeted metabolomics analysis revealed 540 metabolites with significant differential levels. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that these metabolites were mainly enriched in metabolic pathways, including nucleotide metabolism, purine metabolism, arginine biosynthesis, and neuroactive ligand-receptor interaction. Moreover, 134 of 540 metabolites quantified by targeted metabolomics analysis had differential levels and were enriched in metabolic pathways such as the biosynthesis of cofactors, ABC transporters, and biosynthesis of amino acids. Furthermore, coalition analysis of untargeted and targeted metabolomics data revealed that the levels of acylcarnitines, which are intermediates of fatty acid β-oxidation, were significantly increased in ASFV-infected spleens compared with those in the uninfected spleens. Moreover, inhibiting fatty acid β-oxidation significantly reduced ASFV replication, indicating that fatty acid β-oxidation is essential for this process. To our knowledge, this is the first report presenting the metabolite profiles of ASFV-infected pigs. This study revealed a new mechanism of ASFV-mediated regulation of host metabolism. These findings provide new insights into the pathogenic mechanisms of ASFV, which will benefit the development of target drugs for ASFV replication. IMPORTANCE African swine fever virus, the only member of the family, relies on hijacking host metabolism to meet the demand for self-replication. However, the change in host metabolism after African swine fever virus (ASFV) infection remains unknown. Here, we analyzed the metabolic changes in the pig spleen after ASFV infection for the first time. ASFV infection increased the levels of acylcarnitines. Inhibition of the production and metabolism of acylcarnitines inhibited ASFV replication. Acylcarnitines are the vital intermediates of fatty acid β-oxidation. This study highlights the critical role of fatty acid β-oxidation in ASFV infection, which may help identify target drugs to control African swine fever disease.
非洲猪瘟（ASF）是一种由非洲猪瘟病毒（ASFV）引起的毁灭性疾病，对养猪业造成了不利影响。脾脏是 ASFV 的主要靶器官；然而，ASFV 感染期间脾脏中代谢物的功能仍有待研究。为了确定 ASFV 感染后脾脏的代谢变化，对 ASFV 感染猪的脾脏进行了非靶向和靶向代谢组学分析。非靶向代谢组学分析显示有 540 种代谢物具有显著差异水平。京都基因与基因组百科全书途径分析表明，这些代谢物主要富集在代谢途径中，包括核苷酸代谢、嘌呤代谢、精氨酸生物合成和神经活性配体-受体相互作用。此外，通过靶向代谢组学分析定量的 540 种代谢物中有 134 种具有差异水平，并富集在生物合成辅助因子、ABC 转运体和氨基酸生物合成等代谢途径中。此外，非靶向和靶向代谢组学数据的联合分析表明，与未感染的脾脏相比，感染 ASFV 的脾脏中脂肪酸β-氧化的中间产物酰基肉碱的水平显著升高。此外，抑制脂肪酸β-氧化显著降低了 ASFV 的复制，表明脂肪酸β-氧化对这一过程至关重要。据我们所知，这是首次报道 ASFV 感染猪的代谢物谱。本研究揭示了 ASFV 介导的宿主代谢调节的新机制。这些发现为 ASFV 的致病机制提供了新的见解，这将有助于开发针对 ASFV 复制的靶向药物。
非洲猪瘟病毒是唯一的成员，它依赖于劫持宿主代谢来满足自身复制的需求。然而，非洲猪瘟病毒（ASFV）感染后宿主代谢的变化尚不清楚。在这里，我们首次分析了 ASFV 感染后猪脾脏的代谢变化。ASFV 感染增加了酰基肉碱的水平。抑制酰基肉碱的产生和代谢抑制了 ASFV 的复制。酰基肉碱是脂肪酸β-氧化的重要中间产物。本研究强调了脂肪酸β-氧化在 ASFV 感染中的关键作用，这可能有助于确定控制非洲猪瘟疾病的靶标药物。
