U.S. Department of Energy

Pacific Northwest National Laboratory

Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics.

TitleTemporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics.
Publication TypeJournal Article
Year of Publication2010
AuthorsDiamond DL, Syder AJ, Jacobs JM, Sorensen CM, Walters K-A, Proll SC, McDermott JE, Gritsenko MA, Zhang Q, Zhao R, Metz TO, Camp DG, Waters KM, Smith RD, Rice CM, Katze MG
JournalPLoS Pathog
KeywordsCell Line, Tumor, Chromatography, Liquid, Energy Metabolism, Hepacivirus, Humans, Lipids, Liver, Mass Spectrometry, Proteins, Proteome, Virus Replication
Abstract

Proteomic and lipidomic profiling was performed over a time course of acute hepatitis C virus (HCV) infection in cultured Huh-7.5 cells to gain new insights into the intracellular processes influenced by this virus. Our proteomic data suggest that HCV induces early perturbations in glycolysis, the pentose phosphate pathway, and the citric acid cycle, which favor host biosynthetic activities supporting viral replication and propagation. This is followed by a compensatory shift in metabolism aimed at maintaining energy homeostasis and cell viability during elevated viral replication and increasing cellular stress. Complementary lipidomic analyses identified numerous temporal perturbations in select lipid species (e.g. phospholipids and sphingomyelins) predicted to play important roles in viral replication and downstream assembly and secretion events. The elevation of lipotoxic ceramide species suggests a potential link between HCV-associated biochemical alterations and the direct cytopathic effect observed in this in vitro system. Using innovative computational modeling approaches, we further identified mitochondrial fatty acid oxidation enzymes, which are comparably regulated during in vitro infection and in patients with histological evidence of fibrosis, as possible targets through which HCV regulates temporal alterations in cellular metabolic homeostasis.

DOI10.1371/journal.ppat.1000719
Alternate JournalPLoS Pathog.
PubMed ID20062526
PubMed Central IDPMC2796172
Grant List1P30DA01562501 / DA / NIDA NIH HHS / United States
DK70497 / DK / NIDDK NIH HHS / United States
R01CA57073 / CA / NCI NIH HHS / United States
RR018522 / RR / NCRR NIH HHS / United States
U19AI040034 / AI / NIAID NIH HHS / United States
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