Nonstructural protein of Rift Valley Fever Virus is an interferon antagonist subverting innate immunity

Rift Valley fever virus (RVFV) is a major public health threat in Egypt and subsaharan Africa. The viral and host cellular factors that contribute to RVFV pathogenicity are still poorly understood. All pathogenic RVFV strains express a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has a yet undefined accessory function. We have recently discovered that the NSs protein serves as a pathogenicity factor subverting host innate immunity by inhibiting IFN-a/b production. RVFV strains lacking NS induce large amounts of circulating interferon and are highly attenuated in vivo. Interferon activates the Mx system which blocks the growth of RVFV and other bunyaviruses. We want to elucidate the mechanism(s) by which NSs works. This may provide new insights for the development of safe and efficient live virus vaccines and other preventive measures.

Additional information: http://www.UKL.uni-freiburg.de/microbio
contact person: Prof. Dr. Otto Haller
Phone: (0761) 203-6534
Email: otto.haller@uniklinik-freiburg.de

Start of project: 01.10.2000
End of project: (unlimited)

Albert-Ludwigs-University Freiburg
Haller Otto
Department für Medizinische Mikrobiologie und Hygiene
Institut für Virologie
Hermann-Herder-Strasse 11
79104 Freiburg
Germany

Phone: +49 761 203 6534
Fax: +49 761 203 6626
http://www.virologie.uniklinik-freiburg.de
Actual Research Report

• Spiegel M, Weber F, Kochs G, Haller O: How viruses fight the interferon system In: Harald zur Hausen (Hrsg.): Nova Acta Leopoldina, Threat of Infection, 1. Aufl.. Auflage. Halle/Saale: Wisssenschaftl. Verlagsgesellschaft Stuttgart, 2005; 189-197.
• Andersson I, Bladh L, Mousavi-Jazi M, Magnusson KE, Lundkvist Å, Haller O, Mirazimi A: Human MxA protein inhibits replication of Crimean-Congo hemorrhagic fever virus. J Virol, 2004; 78: 4323-4329.
• Bouloy M., Janzen Ch., Vialat P., Khun H., Pavlovic J., Huerre M., Haller O.: Genetic evidence for an interferon-antagonistic function of Rift Valley Fever Virus nonstructural protein NSs. J Virol, 2001; 75 (3): 1371-1377.
• Hefti H.P., Frese M., Landis H., Di Paolo C., Aguzzi A., Haller O., Pavlovic J.: Human MxA protein protexts mice lacking a functional alpha/ beta interferon system against LaCrosse virus and other lethal viral functions. J Virol, 1999; 73: 6984-6991.
• Frese M., Kochs G., Feldmann H., Hertkorn C., Haller O.: Inhibition of bunyaviruses, phleboviruse and hantaviruses by human MxA protein. J. Virol., 1996; 70: 915-923.