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Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis

Genes & Immunity volume 16, pages 261–267 (2015)Cite this article

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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.

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Acknowledgements

This work was supported by grants from the Canadian Institutes of Health Research (CIHR) SAW, GAL and JM were supported by FRSQ Scholarships and SMV by the Canada Research Chair program.

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  1. Department of Human Genetics, McGill University, Montreal, QC, Canada

    S A Wiltshire, J Marton, G A Leiva-Torres & S M Vidal

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  1. S A Wiltshire
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  2. J Marton
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  4. S M Vidal
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Correspondence to S M Vidal.

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Wiltshire, S., Marton, J., Leiva-Torres, G. et al. Mapping of a quantitative trait locus controlling susceptibility to Coxsackievirus B3-induced viral hepatitis. Genes Immun 16, 261–267 (2015). https://doi.org/10.1038/gene.2015.5

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