Glutathione peroxidase protects mice from viral-induced myocarditis

FASEB J. 1998 Sep;12(12):1143-9. doi: 10.1096/fasebj.12.12.1143.

Abstract

Glutathione peroxidase 1 (GPX-1) is a selenium-dependent enzyme with antioxidant properties. Previous investigations determined that mice deficient in selenium developed myocarditis when infected with a benign strain of coxsackievirus B3 (CVB3/0). To determine whether this effect was mediated by GPX-1, mice with a disrupted Gpx1 gene (Gpx1-/-) were infected with CVB3/0. Gpx1-/- mice developed myocarditis after CVB3/0 infection, whereas infected wild-type mice (Gpx1+/+) were resistant. Sequencing of viruses recovered from Gpx1(-/-)-infected mice demonstrated seven nucleotide changes in the viral genome, of which three occurred at the G residue, the most easily oxidized base. No changes were found in virus isolated from Gpx1+/+ mice. These results demonstrate that GPX-1 provides protection against viral-induced damage in vivo due to mutations in the viral genome of a benign virus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Catalase / metabolism
  • Coxsackievirus Infections / genetics
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / physiopathology*
  • Enterovirus B, Human* / genetics
  • Enterovirus B, Human* / isolation & purification
  • Genome, Viral
  • Glutathione Peroxidase / deficiency
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / physiology*
  • Inflammation
  • Liver / enzymology
  • Malondialdehyde / analysis
  • Mice
  • Mice, Knockout
  • Myocarditis / genetics
  • Myocarditis / pathology
  • Myocarditis / virology*
  • Myocardium / enzymology
  • Myocardium / pathology
  • Point Mutation

Substances

  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase