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Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross‐react with virus and cardiac myosin
Author(s) -
Fairweather D.,
Lawson C. M.,
Chapman A. J.,
Brown C. M. S.,
Booth T. W. M.,
Papadimitriou J. M.,
Shellam G. R.
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00500.x
Subject(s) - myocarditis , biology , virology , antibody , virus , viral myocarditis , myosin , monoclonal antibody , autoantibody , microbiology and biotechnology , immunology , medicine , biophysics
The laboratory‐adapted K181 strain of murine cytomegalovirus (MCMV) induces both acute and chronic myocarditis, associated with autoantibodies to cardiac myosin, in susceptible BALB/c mice. However, the K181 MCMV strain has been maintained in the laboratory for many years and may not resemble naturally occurring strains of MCMV in its ability to induce myocarditis. Accordingly, six different isolates of MCMV from wild Mus domesticus were compared with K181 MCMV for their ability to induce myocarditis and autoantibodies to cardiac myosin in BALB/c mice. These isolates were shown to induce acute myocarditis similar to K181 MCMV, with associated focal and diffuse myocardial inflammation. However, the levels of myocarditis induced by the wild isolates during the chronic phase of the disease (days 32–56 post‐infection) were low in contrast to the K181 strain. Interestingly, 30% of wild‐trapped mice showed histological evidence of myocarditis and all were sero‐positive to MCMV. Sera from BALB/c mice infected with wild MCMV isolates and from wild‐trapped mice contained antibodies that cross‐reacted with MCMV and cardiac myosin (S2 region). The cross‐reactive region of MCMV was found to be a 50 000–55 000 MW viral polypeptide. These findings suggest that molecular mimicry may be involved in the pathogenesis of autoimmune myocarditis following infection with both laboratory and wild MCMV strains. EDTA, ethylenediaminetetraacetic acid
ELISA, enzyme‐linked immunosorbent assay
H&E, haematoxylin and eosin
HMM, heavy meromyosin
i.p., intraperitoneal
LMM, light meromyosin
mAb, monoclonal antibodies
MCMV, murine cytomegalovirus
MEF, mouse embryo fibroblasts
MOBS, mouse osmolarity buffered saline
MW, molecular weight
OD, optical density
PBS, phosphate buffered saline
PFU, plaque‐forming units
p.i., post‐infection
PMSF, phenylmethylsulphonyl fluoride
PVDF, polyvinylidene difluoride
SDS–PAGE, sodium dodecyl sulphate–polyacrylamide gel electrophoresis.