Abstract
Several viruses have been demonstrated to be the etiologic agent in chronic progressive diseases, associated with persistence; however, major questions concerning the pathogenic mechanisms of viral persistence are still unanswered. With the aim of identifying host cellular proteins that may play a role in viral replication, we established long-term persistently infected human glioblastoma cell lines with mutant measles virus (MV) and analyzed the host proteins by two-dimensional gel electrophoresis (2-DE) with mass spectrometry. We observed significant down-modulation in the expression of mitochondrial short chain enoyl-CoA hydratase (ECHS), which catalyzes the beta-oxidation pathway of fatty acid. Knockdown of this gene by a short interference RNA (siRNA) apparently impaired wild-type MV replication and the cytopathic effects (CPEs) of MV were significantly reduced in siRNA-transfected cells. These findings will shed light upon a new important notion for the interaction between virus replication and lipid metabolism in host cells and might provide a new strategy for virus control.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / pharmacology
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Blotting, Western
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Carnitine O-Palmitoyltransferase / antagonists & inhibitors
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Carnitine O-Palmitoyltransferase / metabolism
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Cell Line, Tumor
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Down-Regulation
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Electrophoresis, Gel, Two-Dimensional
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Enzyme Inhibitors / pharmacology
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Epoxy Compounds / pharmacology
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Fatty Acid Synthases / genetics
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Fatty Acid Synthases / metabolism*
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Glioblastoma / enzymology
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Glioblastoma / pathology
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Glioblastoma / virology
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Heat-Shock Proteins / metabolism
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Humans
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Interferon-beta / pharmacology
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Measles virus / drug effects
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Measles virus / genetics
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Measles virus / growth & development*
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism*
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Molecular Chaperones / metabolism
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Mutation
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NADH, NADPH Oxidoreductases / genetics
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NADH, NADPH Oxidoreductases / metabolism*
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RNA, Small Interfering / genetics
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Semliki forest virus / drug effects
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Semliki forest virus / growth & development
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Transfection
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Vesicular stomatitis Indiana virus / drug effects
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Vesicular stomatitis Indiana virus / growth & development
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Virus Replication*
Substances
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Antiviral Agents
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Enzyme Inhibitors
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Epoxy Compounds
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Heat-Shock Proteins
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Mitochondrial Proteins
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Molecular Chaperones
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RNA, Small Interfering
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prefoldin
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Interferon-beta
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short chain trans-2-enoyl-CoA reductase
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NADH, NADPH Oxidoreductases
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Carnitine O-Palmitoyltransferase
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Fatty Acid Synthases
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etomoxir