Metabolomic Profile of Hepatitis C Virus-Infected Hepatocytes
| Autor: | Robert P. Mohney, William W. Hall, Elizabeth Kensicki, Barbara Roe |
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| Rok vydání: | 2011 |
| Předmět: |
Time Factors
Gastroenterology and hepatology Hepatitis C virus lcsh:Medicine Hepacivirus Viral diseases Biology medicine.disease_cause Biochemistry Microbiology Virus Hepatitis Metabolomics Cell Line Tumor Virology Metabolome medicine Homeostasis Humans lcsh:Science Phospholipids Liver diseases Sphingolipids Thionucleosides Multidisciplinary Deoxyadenosines Systems Biology lcsh:R Fatty Acids Lipid metabolism Metabolism Lipid Metabolism Hepatitis C Sphingolipid Infectious hepatitis Metabolic pathway Cholesterol Hepatocytes Medicine Infectious diseases lcsh:Q Oxidation-Reduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 8, p e23641 (2011) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0023641 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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