The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice

• Published in: Genes and immunity Vol. 16; no. 3; pp. 206 - 212
• Main Authors: Tokuda, S, Do Valle, T Z, Batista, L, Simon-Chazottes, D, Guillemot, L, Bouloy, M, Flamand, M, Montagutelli, X, Panthier, J-J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2015; Nature Publishing Group
• Subjects: 45/43; 631/208/729/743; 64/60; Analysis; Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; Care and treatment; Causes of; Coccidioidomycosis; Development and progression; Disease Models, Animal; Disease Susceptibility; Encephalitis; Female; Gene Expression; Gene mapping; Genetic aspects; Genetic factors; Genetic Markers; Genetic Predisposition to Disease; Genetic research; Genetic susceptibility; Genome-Wide Association Study; Haplotypes; Health aspects; Hepatitis; Human Genetics; Immunology; Inoculation; Lod Score; Male; Mice; Mortality; Mosquitoes; original-article; Phenotype; Phenotypic variations; Polymorphism, Genetic; Quantitative Trait Loci; Rift Valley fever; Rift Valley Fever - genetics; Rift Valley Fever - mortality; Rift Valley Fever - virology; Rift Valley fever virus; Risk factors; RNA polymerases; Survival; France
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2014.79

The large variation in individual response to infection with Rift Valley fever virus (RVFV) suggests that host genetic determinants play a role in determining virus-induced disease outcomes. These genetic factors are still unknown. The systemic inoculation of mice with RVFV reproduces major pathological features of severe human disease, notably the hepatitis and encephalitis. A genome scan performed on 546 (BALB/c × MBT) F2 progeny identified three quantitative trait loci (QTLs), denoted Rvfs - 1 to Rvfs-3 , that were associated with disease susceptibility in MBT/Pas mice. Non-parametric interval-mapping revealed one significant and two suggestive linkages with survival time on chromosomes 2 ( Rvfs-1 ), 5 ( Rvfs-3 ) and 11 ( Rvfs-2 ) with respective logarithm of odds (LOD) scores of 4.58, 2.95 and 2.99. The two-part model, combining survival time and survival/death, identified one significant linkage to Rvfs-2 and one suggestive linkage to Rvfs-1 with respective LOD scores of 5.12 and 4.55. Under a multiple model, with additive effects and sex as a covariate, the three QTLs explained 8.3% of the phenotypic variance. Sex had the strongest influence on susceptibility. The contribution of Rvfs-1 , Rvfs-2 and Rvfs-3 to survival time of RVFV-infected mice was further confirmed in congenic mice.