Coxsackievirus B3 infection induces anti-flavoprotein antibodies in mice.
Enteroviruses, the most common cause of acute myocarditis, are also supposed aetiological agents of dilated cardiomyopathy. Autoantibodies (anti-M7; Klein & Berg, Clin Exp Immunol 1990; 58:283-92) directed against flavoproteins with covalently bound flavin (alphaFp-Ab; Otto et al., Clin Exp Immunol 1998; 111:541-2) are detected in up to 30% of sera of patients with myocarditis and idiopathic dilated cardiomyopathy (IDCM). Mice inoculated with a myocarditic variant of coxsackievirus B3 (CVB3) were employed to study the occurrence of serum alphaFp-Ab following viral infection. The presence of alphaFp-Ab was analysed by Western blotting with the flavoprotein antigens 6-hydroxy-D-nicotine oxidase (6HDNO) and sarcosine oxidase (SaO). Of 10 sera from CVB3-infected mice, five showed a strong reaction with both antigens. The sera were reactive also to the mitochondrial covalently flavinylated proteins dimethylglycine dehydrogenase and sarcosine dehydrogenase. Sera of non-infected mice did not react with these antigens. A 6HDNO mutant protein with non-covalently bound FAD no longer reacted on Western blots with sera of CVB3-infected mice. Preincubation with FAD abolished or reduced the reaction of the sera with the 6HDNO antigen. At 2 weeks p.i. the alphaFp-Ab were of the IgM and IgG isotypes, at 7 and 9 weeks p.i. of the IgG isotype. The sera of CVB3-infected mice reproduced closely the antigenic specificity of the anti-M7 sera of patients, lending further support to the role of coxsackieviruses in the pathogenesis of IDCM.
Cicek
G
G
Institute of Biochemistry and Molecular Biology, University of Freiburg, Freiburg, Germany.
Vuorinen
T
T
Stähle
I
I
Stepanek
P
P
Freudenberg
N
N
Brandsch
R
R
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003384:Coxsackievirus Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology*; D005182:Flavin-Adenine Dinucleotide / Q000276:immunology; D005420:Flavoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism; D009205:Myocarditis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009500:Neutralization Tests; D010088:Oxidoreductases / Q000276:immunology; D010089:Oxidoreductases, N-Demethylating / Q000276:immunology; D010455:Peptides / Q000276:immunology; D051381:Rats; D050879:Sarcosine Oxidase; D014357:Trypsin / Q000378:metabolism
D001323:Autoantibodies; D005420:Flavoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides; D005182:Flavin-Adenine Dinucleotide; D010088:Oxidoreductases; D010089:Oxidoreductases, N-Demethylating; D050879:Sarcosine Oxidase; C021413:6-hydroxy-D-nicotine oxidase; D014357:Trypsin; D008666:Metalloendopeptidases; C039830:peptidyl-Lys metalloendopeptidase