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THE GENETIC BASIS FOR SUSCEPTIBILITY TO RIFT VALLEY FEVER DISEASE IN MBT/PAS MICE
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Affilliation
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Prtozoologia. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France / Sorbonne Universités. UPMC Univ Paris 06, IFD, F-75006. Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Bunyaviruses Molecular Genetics. F-75015 Paris, France.
Institut Pasteur. Structural Virology. F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Prtozoologia. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France / Sorbonne Universités. UPMC Univ Paris 06, IFD, F-75006. Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Bunyaviruses Molecular Genetics. F-75015 Paris, France.
Institut Pasteur. Structural Virology. F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Institut Pasteur. Developmental & Stem Cell Biology Department. Mouse functional Genetics. F-75015, Paris, France / Centre National de la Recherche Scientifique. URA 2578, F-75015 Paris, France.
Abstract
The large variation in individual response to infection with Rift Valley fever virus
3 (RVFV) suggests that host genetic determinants play a role in determining virus4
induced disease outcomes. These genetic factors are still unknown. The systemic
5 inoculation of mice with RVFV reproduces major pathological features of severe
6 human disease, notably the hepatitis and encephalitis. A genome scan performed
7 on 546 (BALB/c MBT) F2 progeny identified three quantitative trait loci (QTLs),
8 denoted Rvfs-1 to Rvfs-3, that were associated with disease susceptibility in
9 MBT/Pas mice. Non parametric interval-mapping revealed one significant and two
10 suggestive linkages with survival time on chromosomes 2 (Rvfs-1), 5 (Rvfs-3), and
11 11 (Rvfs-2) with respective LOD scores of 4.58, 2.95 and 2.99. The two-part model,
12 combining survival time and survival/death, identified one significant linkage to
13 Rvfs-2 and one suggestive linkage to Rvfs-1 with respective LOD scores of 5.12 and
14 4.55. Under a multiple model, with additive effects and sex as a covariate, the three
15 QTLs explained 8.3 % of the phenotypic variance. Sex had the strongest influence
16 on susceptibility. The contribution of Rvfs-1, Rvfs-2, and Rvfs-3 to survival time of
17 RVFV-infected mice was further confirmed in congenic mice.
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