Dynamics of the Cellular Metabolome during Human Cytomegalovirus Infection

TLDR

Human cytomegalovirus hijacks host cell metabolism, yet the specific alterations in metabolic composition during infection remain poorly understood. We profiled 63 intracellular metabolites over time in HCMV‑infected fibroblasts using LC‑MS/MS, complemented by microarray data on metabolic gene expression. HCMV infection drives marked increases in glycolytic, TCA, and pyrimidine metabolites, with transcriptional upregulation of related enzymes, exceeding levels seen in normal or quiescent fibroblasts and revealing a virus‑specific metabolic program.

Abstract

Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. Despite this reliance, the effect of viral infection on host cell metabolic composition remains poorly understood. Here we applied liquid chromatography-tandem mass spectrometry to measure the levels of 63 different intracellular metabolites at multiple times after human cytomegalovirus (HCMV) infection of human fibroblasts. Parallel microarray analysis provided complementary data on transcriptional regulation of metabolic pathways. As the infection progressed, the levels of metabolites involved in glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis markedly increased. HCMV-induced transcriptional upregulation of specific glycolytic and citric acid cycle enzymes mirrored the increases in metabolite levels. The peak levels of numerous metabolites during infection far exceeded those observed during normal fibroblast growth or quiescence, demonstrating that HCMV markedly disrupts cellular metabolic homeostasis and institutes its own specific metabolic program.