Complex genetic control of host susceptibility to coxsackievirus B3-induced myocarditis.
The pathogenesis of viral myocarditis is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a model of infection with coxsackievirus B3 (CVB3) to characterize the contribution of host genetics to viral myocarditis in mice of different genetic backgrounds but with a common H2 haplotype: A/J and B10.A-H2(a). Here we have used Evans blue dye as a quantitative biomarker for susceptibility to CVB3-induced myocarditis in addition to histopathological semiquantitative measures. We have found evidence of linkage between susceptibility to viral myocarditis and three loci. A locus on chromosome 1 centered on D1Mit200 was linked to sarcolemmal disruption in males (P=0.00005), a second locus on chromosome 4 centered on D4Mit81 was also linked to sarcolemmal disruption in males (P=0.0022). A third locus on distal chromosome 3 centered on D3Mit19 was linked to myocardial infiltration, with a logarithm of odds (LOD) score of 4.7 (P=0.0045), as well as sarcolemmal disruption in females (P=0.0015). These results provide strong evidence for the presence of loci contributing to the susceptibility of mice to viral myocarditis.
Aly
M
M
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Wiltshire
S
S
Chahrour
G
G
Osti
J-C Loredo
JC
Vidal
S M
SM
D000818:Animals; D002874:Chromosome Mapping; D003384:Coxsackievirus Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D029822:Enterovirus B, Human; D005260:Female; D005805:Genes, MHC Class I; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D009205:Myocarditis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D012508:Sarcolemma / Q000473:pathology
D006183:H-2 Antigens