Resistance to Rift Valley fever virus in Rattus norvegicus: genetic variability within certain 'inbred' strains.
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.
Ritter
Marcus
M
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany1.
Bouloy
Michèle
M
Groupe des Bunyaviridés, Unité des Arbovirus et Virus des Fièvres Hèmorragiques, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris, France2.
Vialat
Pierre
P
Groupe des Bunyaviridés, Unité des Arbovirus et Virus des Fièvres Hèmorragiques, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris, France2.
Janzen
Christian
C
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany1.
Haller
Otto
O
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany1.
Frese
Michael
M
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany1.
D000818:Animals; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051381:Rats / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D012295:Rift Valley Fever / Q000235:genetics / Q000276:immunology* / Q000821:virology; D012296:Rift Valley fever virus