Metabolomic analysis of pig spleen reveals African swine fever virus infection increased acylcarnitine levels to facilitate viral replication
文献类型: 外文期刊
第一作者: Yang, Xing
作者: Yang, Xing;Bie, Xintian;Liu, Huanan;Shi, Xijuan;Zhang, Dajun;Zhao, Dengshuai;Hao, Yu;Yang, Jinke;Yan, Wenqian;Chen, Guohui;Chen, Lingling;Zhu, Zixiang;Yang, Fan;Ma, Xusheng;Liu, Xiangtao;Zheng, Haixue;Zhang, Keshan;Zhang, Keshan
作者机构:
关键词: African swine fever virus; spleen; acyl-carnitines; fatty acid beta-oxidation; metabolomics
期刊名称:JOURNAL OF VIROLOGY ( 影响因子:5.4; 五年影响因子:4.9 )
ISSN: 0022-538X
年卷期: 2023 年
页码:
收录情况: SCI
摘要: African swine fever (ASF) is a devastating disease caused by the African swine fever virus (ASFV) that adversely affectsaffects 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 quantifiedquantified 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 beta-oxidation, were significantly increased in ASFV-infected spleens compared with those in the uninfected spleens. Moreover, inhibiting fatty acid beta-oxidation significantlysignificantly reduced ASFV replication, indicating that fatty acid beta-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 Asfarviridae 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 beta-oxidation. This study highlights the critical role of fatty acid beta-oxidation in ASFV infection, which may help identify target drugs to control African swine fever disease.
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