Metabolic Profiles in Madin-Darby Canine Kidney Cell Lines Infected with H3N2 Canine Influenza Viruses.

Abstract

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.