Molecular mimicry, anti-coxsackievirus B3 neutralizing monoclonal antibodies, and myocarditis.
Molecular mimicry has been suggested as one mechanism to explain chronic myocarditis in some murine strains in the postinfectious period following induction of acute myocarditis by coxsackievirus B3 (CVB3). To test this hypothesis, neutralizing mAbs were generated against a highly myocarditic CVB3 virus (CVB3m). These mAbs neutralized several myocarditic and amyocarditic CVB3 variants by cytopathic effects inhibition assays. Data from several experiments suggest that these mAbs recognize discontinuous epitopes on CVB3m capsid proteins. Several mAbs were found to induce cardiopathologic alterations subsequent to i.p. inoculation of normal adolescent male CD-1 or C3H/HeJ mice. Immunocytochemical assays demonstrated significant binding of two mAbs to the surface of normal cultured murine cardiac fibroblasts. Also, several mAbs were shown to participate in C-mediated lysis of normal cardiac fibroblasts, but this property did not correlate well with cardiopathogenic potential. The two properties of a mAb that were the best predictors for cardiopathogenic potential were the capacity for stimulation of normal murine fibroblasts to produce a chemoattractant activity for unelicted murine peritoneal macrophages, and the capacity for recognition of an epitopes(s) on murine or human cardiac myosins. These data show that some anti-CVB3m neutralizing mAbs can participate in proinflammatory reactions in vitro and induce cardiopathologic alterations in vivo, suggesting one mechanism by which CVB3-induced chronic inflammation in murine heart tissues can be sustained in the absence of continued virus replication.
Gauntt
C J
CJ
Department of Microbiology, University of Texas, Health Science Center at San Antonio, 78284.
Arizpe
H M
HM
Higdon
A L
AL
Wood
H J
HJ
Bowers
D F
DF
Rozek
M M
MM
Crawley
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D029822:Enterovirus B, Human / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology; D009205:Myocarditis / Q000209:etiology* / Q000276:immunology / Q000821:virology; D009206:Myocardium / Q000276:immunology*; D009500:Neutralization Tests; D011233:Precipitin Tests
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes