title: Metabolomic profile of hepatitis C virus-infected hepatocytes.
abstract: Hepatitis C virus (HCV) is capable of disrupting different facets of lipid metabolism and lipids have been shown to play a crucial role in the viral life cycle. The aim of this study was to examine the effect HCV infection has on the hepatocyte metabolome. Huh-7.5 cells were infected using virus produced by the HCV J6/JFH1 cell culture system and cells were harvested 24, 48, and 72-hours following infection. Metabolic profiling was performed using a non-targeted multiple platform methodology combining ultrahigh performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS(2)) and gas chromatography/mass spectrometry (GC/MS). There was a significant increase in a number of metabolites involved in nucleotide synthesis and RNA replication during early HCV infection. NAD levels were also significantly increased along with several amino acids. A number of lipid metabolic pathways were disrupted by HCV infection, resulting in an increase in cholesterol and sphingolipid levels, altered phospholipid metabolism and a possible disruption in mitochondrial fatty acid transport. Fluctuations in 5'-methylthioadenosine levels were also noted, along with alterations in the glutathione synthesis pathway. These results highlight a number of previously unreported metabolic interactions and give a more in depth insight into the effect HCV has on host cell biochemical processes.
authors.affiliation: Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin, Ireland. barbara.roe@ucd.ie
authors.forename: Barbara
authors.initials: B
authors.lastname: Roe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kensicki
authors.forename: Robert
authors.initials: R
authors.lastname: Mohney
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
mesh_terms: D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology*; D022781:Hepatocytes / Q000378:metabolism* / Q000821:virology*; D006706:Homeostasis; D006801:Humans; D055432:Metabolomics; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism; D013872:Thionucleosides / Q000378:metabolism; D013997:Time Factors
chemical_list: D003839:Deoxyadenosines; D005227:Fatty Acids; D010743:Phospholipids; D013107:Sphingolipids; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D002784:Cholesterol