Anti-Coxsackievirus B3 neutralizing antibodies with pathological potential.
Adolescent CD-1 mice inoculated with coxsackievirus B3 (CVB3m) will develop acute myocarditis with focal lesions by 7 days post-inoculation (p.i.). Administration of murine sera containing anti-CVB3m-neutralizing antibodies into CVB3m-inoculated mice at 3 days p.i. will exacerbate myocarditis, suggesting the presence of pathological antibodies. To study potential pro-inflammatory properties of virus-induced antibodies, a panel of anti-CVB3m-neutralizing monoclonal antibodies (mAbs) was generated. Several studies demonstrated shared epitopes between CVB3m particles and cultured murine cardiac or neonatal skin fibroblasts: (1) one or more mAbs bound to cultured cardiac fibroblasts; (2) several mAbs can participate in complement-mediated lysis of neonatal skin fibroblasts; and (3) at least one mAbs stimulated synthesis of a macrophage chemoattractant from cultured neonatal skin fibroblasts. Injection of one mAb in three doses, each of about 5 micrograms, into adolescent male CD-1 mice induced focal myocarditic lesions which were similar to CVB3m-induced lesions. One mAb induced a diffuse interstitial hypercellularity in most mice and two mAbs did not induce detectable cardiopathology. These data suggest that some anti-CVB3m neutralizing idiotypes (antibodies) which initially can provide protection via virus clearance mechanisms can also bind to cross-reacting epitopes on normal tissues. Binding of antibodies to normal heart tissues could stimulate proinflammatory reactions by several mechanisms and sustain myocarditis.
Gauntt
C J
CJ
Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
Arizpe
H M
HM
Higdon
A L
AL
Rozek
M M
MM
Crawley
R
R
Cunningham
M W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015151:Immunoblotting; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000276:immunology / Q000382:microbiology; D009206:Myocardium / Q000276:immunology; D009218:Myosins / Q000276:immunology; D012867:Skin / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D009218:Myosins