Coxsackievirus B3-induced chronic myocarditis in outbred NMRI mice.
OBJECTIVE
The pathogenesis of coxsackievirus B3 (CVB3)-induced myocarditis was investigated in adult Han:NMRI mice. The outbred model, in comparison with inbred models, represents better the natural variable susceptibility of the human population.


METHODS
We analyzed the replicating virus titer, the antibody response in the acute and chronic phase of disease, the histology of myocardial injury, and the persistence of viral RNA.


RESULTS
NMRI mice infected with 5000 plaque-forming units (PFU) of the CVB3 variant "P"D, a lytic variant to human fibroblast lines, showed a peak of virus replication at day 14 and developed a severe acute myocarditis. The chronic myocarditis was characterized by progressive fibrosis, small foci of infiltrates, persistent viral RNA in the heart, and detectable anti-CVB3 IgG production and neutralizing antibody response up to day 98 postinfection.


CONCLUSIONS
CVB3"P"D is able to induce chronic myocarditis in NMRI mice. This model provides a method for examining and proving the mechanisms of myocardial pathogenesis and of developing therapeutic strategies.
Merkle
I
I
Institute of Virology, Clinical Center of the Friedrich Schiller University, Jena, Germany. I8MEIN@pop3.uni-jena.de
Tonew
M
M
Glück
B
B
Schmidtke
M
M
Egerer
R
R
Stelzner
A
A
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D006321:Heart / Q000821:virology; D006801:Humans; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000473:pathology; D010179:Pancreas / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication
D000914:Antibodies, Viral; D012367:RNA, Viral