Glutathione peroxidase 1 (GPX-1) is a selenium-dependent enzyme with a
ntioxidant properties, Previous investigations determined that mice de
ficient 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 (Glbx1(-/-)) w
ere infected with CVB3/0, Gpx1(-/-) mice developed myocarditis after C
VB3/0 infection, whereas infected wild-type mice (Gpx1(+/+)) were resi
stant. Sequencing of viruses recovered from Gpx1(-/-)-infected mice de
monstrated seven nucleotide changes in the viral genome, of which thre
e occurred at the G residue, the most easily oxidized base, No changes
were found in virus isolated from Gpx1(+/+) mice. These results demon
strate that GPX-1 provides protection against viral-induced damage in
vivo due to mutations in the viral genome of a benign virus.