Suppression of virus replication via down-modulation of mitochondrial short chain enoyl-CoA hydratase in human glioblastoma cells

Antiviral Res. 2007 Aug;75(2):152-8. doi: 10.1016/j.antiviral.2007.02.002. Epub 2007 Mar 16.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Blotting, Western
  • Carnitine O-Palmitoyltransferase / antagonists & inhibitors
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme Inhibitors / pharmacology
  • Epoxy Compounds / pharmacology
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism*
  • Glioblastoma / enzymology
  • Glioblastoma / pathology
  • Glioblastoma / virology
  • Heat-Shock Proteins / metabolism
  • Humans
  • Interferon-beta / pharmacology
  • Measles virus / drug effects
  • Measles virus / genetics
  • Measles virus / growth & development*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Chaperones / metabolism
  • Mutation
  • NADH, NADPH Oxidoreductases / genetics
  • NADH, NADPH Oxidoreductases / metabolism*
  • RNA, Small Interfering / genetics
  • Semliki forest virus / drug effects
  • Semliki forest virus / growth & development
  • Transfection
  • Vesicular stomatitis Indiana virus / drug effects
  • Vesicular stomatitis Indiana virus / growth & development
  • Virus Replication*

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Epoxy Compounds
  • Heat-Shock Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • RNA, Small Interfering
  • prefoldin
  • Interferon-beta
  • short chain trans-2-enoyl-CoA reductase
  • NADH, NADPH Oxidoreductases
  • Carnitine O-Palmitoyltransferase
  • Fatty Acid Synthases
  • etomoxir