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Resistance to Rift Valley fever virus in Rattus norvegicus: genetic variability within certain ‘inbred’ strains

Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany¹
Groupe des Bunyaviridés, Unité des Arbovirus et Virus des Fièvres Hèmorragiques, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris, France²

Author for correspondence: Michael Frese. Fax +49 761 203 6626. e-mail frese{at}ukl.uni-freiburg.de

Rift Valley fever virus (RVFV) is the causative agent of Rift Valley fever, a widespread disease of domestic animals and humans in sub-Saharan Africa. Laboratory rats have frequently been used as an animal model for studying the pathogenesis of Rift Valley fever. It is shown here that Lewis rats (LEW/mol) are susceptible to infection with RVFV, whereas Wistar–Furth (WF/mol) rats are resistant to RVFV infection. LEW/mol rats developed acute hepatitis and died after infection with RVFV strain ZH548, whereas WF/mol rats survived the infection. Cross-breeding of resistant WF/mol rats with susceptible LEW/mol rats demonstrated that resistance is segregated as a single dominant gene. Primary hepatocytes but not glial cells from WF/mol rats showed the resistant phenotype in cell culture, indicating that resistance was cell type-specific. Moreover, when cultured hepatocytes were stimulated with interferon (IFN) type I there was no indication of a regulatory role of IFN in the RVFV-resistance gene expression in WF/mol rats. Interestingly, previous reports have shown that LEW rats from a different breeding stock (LEW/mai) are resistant to RVFV infections, whereas WF/mai rats are susceptible. Thus, inbred rat strains seem to differ in virus susceptibility depending on their breeding histories. A better genetic characterization of inbred rat strains and a revision in nomenclature is needed to improve animal experimentation in the future.

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				B. H. Bird, M. L. Khristova, P. E. Rollin, T. G. Ksiazek, and S. T. Nichol Complete Genome Analysis of 33 Ecologically and Biologically Diverse Rift Valley Fever Virus Strains Reveals Widespread Virus Movement and Low Genetic Diversity due to Recent Common Ancestry J. Virol., March 15, 2007; 81(6): 2805 - 2816. [Abstract] [Full Text] [PDF]