title: The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice.
abstract: 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.
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Tokuda
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France [3] Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia, Fiocruz, Rio de Janeiro, Brasil.
authors.forename: T Z
authors.initials: TZ
authors.lastname: Do Valle
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France [3] Sorbonne Universités, UPMC Univ Paris 06, IFD, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Batista
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Simon-Chazottes
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Guillemot
authors.affiliation: Institut Pasteur, Bunyaviruses Molecular Genetics, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bouloy
authors.affiliation: Institut Pasteur, Structural Virology, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Flamand
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Montagutelli
authors.affiliation: 1] Institut Pasteur, Developmental & Stem Cell Biology Department, Mouse functional Genetics, Paris, France [2] Centre National de la Recherche Scientifique, URA 2578, Paris, France.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Panthier
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D008126:Lod Score; D008297:Male; D051379:Mice; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012295:Rift Valley Fever / Q000235:genetics* / Q000401:mortality / Q000821:virology*; D012296:Rift Valley fever virus
chemical_list: D005819:Genetic Markers