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 me...

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Main Authors: Joshua Munger, Sunil U Bajad, Hilary A Coller, Thomas Shenk, Joshua D Rabinowitz
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2006-12-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC1698944?pdf=render
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author Joshua Munger
Sunil U Bajad
Hilary A Coller
Thomas Shenk
Joshua D Rabinowitz
author_facet Joshua Munger
Sunil U Bajad
Hilary A Coller
Thomas Shenk
Joshua D Rabinowitz
author_sort Joshua Munger
collection DOAJ
description 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.
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spelling doaj.art-4d830864b70c4767921adbd501d0d3052022-12-22T01:29:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742006-12-01212e13210.1371/journal.ppat.0020132Dynamics of the cellular metabolome during human cytomegalovirus infection.Joshua MungerSunil U BajadHilary A CollerThomas ShenkJoshua D RabinowitzViral 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.http://europepmc.org/articles/PMC1698944?pdf=render
spellingShingle Joshua Munger
Sunil U Bajad
Hilary A Coller
Thomas Shenk
Joshua D Rabinowitz
Dynamics of the cellular metabolome during human cytomegalovirus infection.
PLoS Pathogens
title Dynamics of the cellular metabolome during human cytomegalovirus infection.
title_full Dynamics of the cellular metabolome during human cytomegalovirus infection.
title_fullStr Dynamics of the cellular metabolome during human cytomegalovirus infection.
title_full_unstemmed Dynamics of the cellular metabolome during human cytomegalovirus infection.
title_short Dynamics of the cellular metabolome during human cytomegalovirus infection.
title_sort dynamics of the cellular metabolome during human cytomegalovirus infection
url http://europepmc.org/articles/PMC1698944?pdf=render
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