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

Genes & Immunity volume 16, pages 206–212 (2015)Cite this article

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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.

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Acknowledgements

We thank Rashida Lathan for reading the manuscript and editorial suggestions. We are grateful to all members of the laboratory for technical advice and helpful discussion. Genotyping of F2 mice was performed by the Centre National de Génotypage (Evry, France). This work was supported by the Agence Nationale de la Recherche (grant n° 11-BSV3-007 01, ‘GenRift’) and the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (grant n°ANR-10-LABX-62-IBEID). The Mouse functional Genetics unit at the Institut Pasteur was funded by Merck-Serono. ST was awarded postdoctoral fellowships from the Pasteur Japan association, and the Region Ile-de-France (DIM Malinf 2010). We thank Direction Générale de l′Armement (DGA) (representative: Emmanuelle Guillot-Combe) for a financial support to LB.

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Author notes

  1. S Tokuda and T Z Do Valle: These authors contributed equally to this work.

Authors and Affiliations

  1. Developmental & Stem Cell Biology Department, Institut Pasteur, Mouse functional Genetics, Paris, France

    S Tokuda, T Z Do Valle, L Batista, D Simon-Chazottes, L Guillemot, X Montagutelli & J-J Panthier

  2. Centre National de la Recherche Scientifique, URA 2578, Paris, France

    S Tokuda, T Z Do Valle, L Batista, D Simon-Chazottes, L Guillemot, X Montagutelli & J-J Panthier

  3. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia, Fiocruz, Rio de Janeiro, Brasil

    T Z Do Valle

  4. Sorbonne Universités, UPMC Univ Paris 06, IFD, Paris, France

    L Batista

  5. Institut Pasteur, Bunyaviruses Molecular Genetics, Paris, France

    M Bouloy

  6. Institut Pasteur, Structural Virology, Paris, France

    M Flamand

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Tokuda, S., Do Valle, T., Batista, L. et al. The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice. Genes Immun 16, 206–212 (2015). https://doi.org/10.1038/gene.2014.79

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