title: Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis.
abstract: The pathogenesis of coxsackieviral infection is a multifactorial process involving host genetics, viral genetics and the environment in which they interact. We have used a mouse model of Coxsackievirus B3 infection to characterize the contribution of host genetics to infection survival and to viral hepatitis. Twenty-five AcB/BcA recombinant congenic mouse strains were screened. One, BcA86, was found to be particularly susceptible to early mortality; 100% of BcA86 mice died by day 6 compared with 0% of B6 mice (P=0.0012). This increased mortality was accompanied by an increased hepatic necrosis as measured by serum alanine aminotransferase (ALT) levels (19547±10556 vs 769±109, P=0.0055). This occurred despite a predominantly resistant (C57BL/6) genetic background. Linkage analysis in a cohort (n=210) of (BcA86x C56Bl/10)F2 animals revealed a new locus on chromosome 13 (peak linkage 101.2 Mbp, lod 4.50 and P=0.003). This locus controlled serum ALT levels as early as 48 h following the infection, and led to an elevated expression of type I interferon. Another locus on chromosome 17 (peak linkage 57.2 Mbp) was significantly linked to heart viral titer (lod 3.4 and P=0.046). These results provide new evidence for the presence of genetic loci contributing to the susceptibility of mice to viral hepatitis.
authors: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors: S A
authors: SA
authors: Wiltshire
authors: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors: J
authors: J
authors: Marton
authors: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors: G A
authors: GA
authors: Leiva-Torres
authors: Department of Human Genetics, McGill University, Montreal, QC, Canada.
authors: S M
authors: SM
authors: Vidal
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics; D000818:Animals; D003384:Coxsackievirus Infections / Q000235:genetics*; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006524:Hepatitis, Viral, Animal / Q000235:genetics*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci
chemical_list: D007370:Interferon Type I; D000410:Alanine Transaminase