Virus replication and host cell growth require host cell metabolic networks to provide energy and precursors for the synthesis of macromolecules. The aim of this study was to investigate the most direct changes in energy metabolism and small-molecule metabolism of Madin–Darby canine kidney (MDCK) cells infected with H3N2 canine influenza virus (CIV) and to determine whether small metabolites contribute to the pathogenesis of CIV. To study the metabolomics of MDCK cells infected with H3N2 CIV, we used liquid chromatography–tandem mass spectrometry combined with multivariate statistical analysis. The results showed that 798 positive ions were detected, among which 33 were upregulated and 11 were downregulated, and 406 negative ions were detected, among which 33 were upregulated and 9 were downregulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that these differentially expressed molecules were mainly concentrated in the steroid hormone biosynthesis, amino sugar and nucleotide sugar metabolism, sphingolipid metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, vitamin digestion and absorption, arginine and proline metabolism, biosynthesis of amino acids, and folate biosynthesis metabolic pathways. These pathways are involved in energy metabolism and nucleic acid and protein synthesis, which are essential for virus replication. Our experimental data suggest that H3N2 CIV infection reconstitutes/influences cellular metabolic processes, which in turn may contribute to viral replication. These findings are important for the development of enzyme inhibitors or metabolites for the identification of antiviral drugs. In addition, understanding the metabolic interaction between CIV and host cells is also very important for the complex pathogenicity of CIV, providing certain guidance for the treatment of canine influenza.

中文翻译：

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感染 H3N2 犬流感病毒的 Madin-Darby 犬肾细胞系的代谢特征

病毒复制和宿主细胞生长需要宿主细胞代谢网络为大分子的合成提供能量和前体。本研究的目的是研究感染 H3N2 犬流感病毒 (CIV) 的 Madin-Darby 犬肾 (MDCK) 细胞的能量代谢和小分子代谢的最直接变化，并确定小代谢物是否有助于发病机制。公民身份。为了研究感染 H3N2 CIV 的 MDCK 细胞的代谢组学，我们使用液相色谱-串联质谱结合多变量统计分析。结果表明，检测到798个正离子，其中上调33个，下调11个；检测到负离子406个，其中上调33个，下调9个。通过京都基因和基因组百科全书（KEGG）富集分析，我们发现这些差异表达的分子主要集中在类固醇激素生物合成、氨基糖和核苷酸糖代谢、鞘脂代谢、维生素B6代谢、半胱氨酸和蛋氨酸代谢、维生素消化和吸收、精氨酸和脯氨酸代谢、氨基酸生物合成和叶酸生物合成代谢途径。这些途径涉及能量代谢以及核酸和蛋白质合成，这些对病毒复制至关重要。我们的实验数据表明，H3N2 CIV 感染重建/影响细胞代谢过程，这反过来可能有助于病毒复制。这些发现对于开发酶抑制剂或代谢物以鉴定抗病毒药物具有重要意义。此外，了解CIV与宿主细胞之间的代谢相互作用对于CIV复杂的致病性也非常重要，为犬流感的治疗提供一定的指导。