Dynamics of the cellular metabolome during human cytomegalovirus infection.
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.
Munger
Joshua
J
Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Bajad
Sunil U
SU
Coller
Hilary A
HA
Shenk
Thomas
T
Rabinowitz
Joshua D
JD
D002478:Cells, Cultured; D002853:Chromatography, Liquid; D002952:Citric Acid Cycle / Q000502:physiology; D003587:Cytomegalovirus / Q000472:pathogenicity* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D006019:Glycolysis / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D011742:Pyrimidine Nucleotides / Q000096:biosynthesis; D053719:Tandem Mass Spectrometry; D014779:Virus Replication / Q000502:physiology
D011742:Pyrimidine Nucleotides