Suppression of virus replication via down-modulation of mitochondrial short chain enoyl-CoA hydratase in human glioblastoma cells.
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.
Takahashi
Megumi
M
Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Watari
Eiji
E
Shinya
Eiji
E
Shimizu
Takako
T
Takahashi
Hidemi
H
D000998:Antiviral Agents / Q000494:pharmacology; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology / Q000821:virology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D008459:Measles virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012672:Semliki forest virus / Q000187:drug effects / Q000254:growth & development; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000254:growth & development; D014779:Virus Replication
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D006360:Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; C112806:prefoldin; D016899:Interferon-beta; C036543:short chain trans-2-enoyl-CoA reductase; D009247:NADH, NADPH Oxidoreductases; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; C054207:etomoxir