Identification of cellular components involved in the antiviral activity of Mx GTPases.

Mx proteins are large GTPases that are induced by type I interferons and have antiviral activity against RNA viruses. The murine Mx1 protein is active against members of the family Orthomyxoviridae, such as influenza virus and Thogoto virus. To better understand the antiviral mechanism of Mx1 protein, we started a search for cellular proteins capable of interacting with Mx1. Using the yeast two-hybrid system, we identified a number of nuclear proteins that are candidate interaction partners of Mx1. Interestingly, three of these candidates are components of PML nuclear bodies (NBs) (also known as PML oncogenic domains or ND10), namely SP100, SUMO-1 and Ubc9. In addition, we recently described a novel Mx-interacting serine/threonine kinase (PKM) that accumulates in NBs and colocalizes with Mx1. Moreover, Mx1 interacts with two enzymes known to be involved in sumoylation of proteins. The aim of this project is to define the role of these cellular partner proteins for Mx1 action.

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

Start of project: 01.10.2000
End of project: 30.09.2003

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

• Deutsche Forschungsgemeinschaft, DFG

Mx-GTPase, PML-Nuclear Bodies, Orthomyxoviridae

• Engelhardt O, Ullrich E, Kochs G, Haller O.: Interferon-induced antiviral Mx1 GTPase is associated with components of the SUMO-1 system and promyelocytic leukemia protein nuclear bodies. Exp Cell Res, 2001; 271: 286-295.
• Trost M., Kochs G., Haller O.: Characterization of a Novel Serine/Threonin Kinase associated with nuclear bodies. J Biol Chem, 2000; 275: 7373-7377.