Pathological and genetic analysis of host susceptibility to cardiovirulent coxsackievirus B3 infection in mice

Abstract

Nearly fifty percent of North American myocarditis cases are associated to coxsackievirus group B, type 3 (CVB3) infection. CVB3 infection of mice provides a useful model to study pathogenic mechanism of myocarditis. The objective of this study is to test the hypothesis that susceptibility, during the acute CVB3 infection, is under polygenic control including H2 as well as the non H-2 genes. To identify differential parameters of the disease, and if they are influenced by the H-2 haplotype, several phenotypic traits were characterized. Three inbred strains of mice and two congenic strains were infected with CVB3. Differences in survival, body weight loss, quantification of myocarditis and quantification of sarcolemmal disruption were found by comparing three sets of mice sharing the same H-2 haplotype but not the same background. It was determined that host susceptibility to CVB3-induced myocarditis is mainly controlled by "background" genes. Moreover, because there is a naturally occurring variability among inbred mice, ten inbred strains of mice were used for the genetic analysis of four CVB3-induced phenotypes: survival, body weight loss, heart viral load and quantification of sarcolemmal disruption. It was concluded that the strains could be divided into three groups: the highly resistant, the resistant to intermediate strains and the highly susceptible strains. This phenotypic data on commonly used and genetically diverse inbred mouse strains sets up the platform for a detailed analysis of the genetic basis of susceptibility to CVB3.