Genetic control of mouse cytomegalovirus-induced myocarditis.
Mouse cytomegalovirus (MCMV) infection of mice induced myocarditis, characterized by a mononuclear cell infiltrate with associated necrosis of myofibres. Myocarditis was observed in parallel with viral inclusion-bearing cells in the heart during the acute phase of the infection. Myocarditis also persisted after the acute phase when viral antigens were no longer detectable by immunoperoxidase histochemistry and infectious virus could not be cultivated from various organs. The influence of host genetic factors on the development of cytomegalovirus-induced myocarditis was investigated using H-2 congenic and recombinant inbred mouse strains. Analysis of congenic variants with C57BL/10 and BALB/c backgrounds and the A/J strain revealed that genes linked to the H-2 complex influenced susceptibility to peak levels of MCMV-induced myocarditis seen 7 and 10 days post-infection. In addition, non-H-2 genes of the BALB/c background were important in determining the severity of myocarditis. Analysis of the strain distribution pattern of the CXB recombinant inbred series did not disclose the identity of the BALB/c non-H-2-linked allele conferring susceptibility to MCMV-induced myocarditis. The level of myocarditis seen in the F1 hybrid between the high-responder BALB/c and low-responder C57BL/6 strains suggested dominant inheritance. The amount of viral replication in the major target organs did not correlate with the severity of myocarditis. In conclusion, at least two genes, one mapping to the H-2 complex and another non-H-2-linked gene, influenced the development of myocarditis in MCMV-infected mice.
Lawson
C M
CM
Department of Medicine, University of Western Australia, Nedlands.
O'Donoghue
H
H
Bartholomaeus
W N
WN
Reed
W D
WD
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000235:genetics*; D005260:Female; D005796:Genes / Q000502:physiology*; D005805:Genes, MHC Class I / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D007124:Immunoenzyme Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000209:etiology / Q000235:genetics*
D000956:Antigens, Viral; D006183:H-2 Antigens