Role of Interferon-induced Mx proteins in natural resistance against RNA viruses.

Virus growth relies on cellular functions such as intracellular transport of macromolecules. For example, influenza viruses need to get their RNA genomes into the nucleus for transcription and replication. Using Thogoto virus, an influenza-like orthomyxovirus, we could show that the interferon-induced MxA protein binds to the viral nucleocapsids in the cytoplasm and blocks their normal movement into the nucleus, which is the place of viral transcription and replication. In the case of bunyaviruses, we could demonstrate that MxA sequesters the viral nucleocapsid protein into large perinuclear complexes. By depleting the cells from newly synthesised nucleocapsid protein, MxA prevents bunyavirus multiplication. Mx proteins belong to the newly defined superfamily of dynamin-like high-molecular-weight GTPases. The aim of the project is to demonstrate the physical interaction between Mx proteins and the viral nucleocapsids by electron microscopy and to identify the interacting protein domains and cellular cofactors involved in the antiviral effect.

Additional information: http://www.UKL.uni-freiburg.de/microbio
contact person: PD Dr. Georg Kochs
Phone: (0761) 203-6623
Email: georg.kochs@uniklinik-freiburg.de

Start of project: 01.08.1997
End of project: 31.12.2008

Albert-Ludwigs-University Freiburg
Kochs Georg, 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

• Deutsche Forschungsgemeinschaft, DFG

Mx Proteine, antiviral, Interferon-induced, large GTPasen, Dynamin-like GTPases

• Reichelt M, Stertz S, Krijnse-Locker J, Haller O, Kochs G: Missorting of LaCrosse virus nucleocapsid protein by the interferon-induced MxA GTPase involves smooth ER membranes. Traffic, 2004; 5: 772-784.
• Haller O, Kochs G: Interferon-induced Mx Proteins: Dynamin-like GTPases with antiviral activity: Traffic, 2002; 3: 710-717.
• Kochs G, Haener M, Aebi U, Haller O.: Self-assembly of human MxA GTPase into highly ordered dynamin-like oligomers. J Biol Chem, 2002; 277: 14172-14176.
• Kochs G, Janzen Ch, Hohenberg H, Haller O.: Antivirally active MxA protein sequesters La Crosse virus nucleocapsid protein into perinuclear complexes. P Natl Acad Sci Usa, 2002; 99: 3153-3158.
• Weber F., Haller O., Kochs G.: MxA GTPase blocks reporter gene expression of reconstituted Thogoto Virus ribonucleoprotein complexes. J Virol, 2000; 74: 560-563.