Integration of Transcriptomics and Metabolomics Reveals Metabolism Dysregulation in HIV-1-Infected Macrophages

HIV-1 infection leads to metabolic changes in macrophages, yet a comprehensive understanding of its pathogenesis remains limited. To address this, we integrated transcriptomic and metabolomic analyses to uncover intracellular metabolic alterations in HIV-1-infected macrophages. We identified differentially expressed genes (DEGs) using RNA-sequencing, while metabolomic profiling was performed with UHPLC-QE-MS. The integration of transcriptomics and metabolomics was achieved through "Joint Pathway Analysis," and reverse transcription-quantitative PCR (RT-qPCR) was used to validate the identified pathways. Our transcriptomic analysis revealed a total of 890 DEGs, comprising 424 downregulated and 466 upregulated genes in macrophages infected with HIV-1. KEGG enrichment analysis highlighted the biosynthesis of amino acids and glycine, serine, and threonine metabolism as significantly enriched (P < 0.05). RT-qPCR results confirmed the expression of key genes, including PHGDH, PSAT1, PSPH, CBS, CTH, and AOC2, associated with these pathways. From the metabolomic analysis, we identified 60 differential metabolites, with glycerophospholipids representing the majority (51.67%). The integrated analysis revealed significant changes in glycine, serine, and threonine metabolism, glycerophospholipid metabolism, and linoleic acid metabolism in HIV-1-infected macrophages. This study offers an extensive overview of metabolic alterations in HIV-1-infected macrophages, which may enhance our understanding of the pathogenesis and highlight potential therapeutic targets.