Grant: Master's Award: Canada Graduate Scholarships

Coxsackievirus B3 (CVB3) infection is a prominent cause of myocarditis, an inflammatory disorder of the myocardium and a frequent cause of acquired heart failure in children. The extent of pathogenesis among exposed individuals is dictated by a combination of host genetics, viral determinants, and the environment. The importance of host genetics, in particular, is highlighted by studies in the mouse model wherein inbred strains differ in their susceptibility to CVB3-induced pathology. To further elucidate the mechanisms that shape the outcome of infection, we have screened a set of recombinant congenic mouse lines derived from second generation backcrossing of A/J and C57BL/6 (B6) mice. We have identified a deviant strain, BcA86, which exhibits increased susceptibility despite its predominantly resistant B6 genetic makeup. Further characterization found that BcA86 mice display significantly increased serum alanine aminotransferaste levels, implicating liver damage in the susceptibility phenotype. Subsequent analysis of a segregating (BcA86xC57BL/10)F2 cross identified a single locus associated with altered susceptibility to CVB3 infection. Investigation of genes underlying the locus identified several candidates. Additional research into the gene and protein expression of the candidates may reveal new genes/pathways involved in CVB3-associated disease and provide further insight into the mechanisms of early host defence to viral infection.