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MxGTPase: Mediator of influenza virus resistance in mice
Mice are frequently used as an animal model to study the pathogenesis of influenza A viruses However, standard laboratory mice do not possess a complete antiviral defense system, as they carry defective alleles of the Mx1 gene. Consequently, mice carrying a wild-type Mx1 gene (Mx1+/+) differ from standard laboratory mice (Mx1−/−) in being highly resistant to infection with influenza A virus. The Mx1 gene is under tight transcriptional control of alpha/beta interferon (IFN-α/β) and codes for a nuclear 72-kDa protein which represents a decisive antiviral factor that controls influenza virus infections in mice.
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| Health status of mice expressing (Mx1+/+) or lacking (Mx1-/-) functional alleles of the influenza virus resistance gene Mx1 at 4 days post infection with influenza A virus. |
Open questions presently being investigated include:
a) Structural and functional analysis of Mx genes from wild mice
b) Viral resistance of transgenic mice expressing Mx gene of human origin
Selected Publications from our group
- Grimm D, Staeheli P, Hufbauer M, Koerner I, Martínez-Sobrido L, Solórzano A, García-Sastre A, Haller O, Kochs G. Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc. Natl. Acad. Sci. USA 104: 6806-6811 (2007).
- Tumpey T, Szretter KJ, van Hoeven N, Katz JM, Kochs G, Haller O, García-Sastre A, Staeheli P. The Mx1 gene protects mice against pandemic 1918 and highly lethal human H5N1 influenza viruses. J. Virol. 81: 10818-10821 (2007)
Collaboration
Prof. Otto Haller and Prof. Georg Kochs, Dept. of Virology, University Medical Center Freiburg
