Glutathione peroxidase protects mice from viral-induced myocarditis.
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.
Beck
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Frank Porter Graham Child Development Center, University of North Carolina at Chapel Hill, 27599-8180, USA. melinda_beck@unc.edu
Esworthy
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Ho
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Chu
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D000818:Animals; D002374:Catalase / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D029822:Enterovirus B, Human / Q000235:genetics / Q000302:isolation & purification; D016679:Genome, Viral; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007249:Inflammation; D008099:Liver / Q000201:enzymology; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000235:genetics / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D017354:Point Mutation
D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase