Antiviral function of the human MxA protein and its association with the viral nucleocapsid

• Applicant: Professor Dr. Georg Kochs
• Subject Area: Virology
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 186108321

The aim of this study is to define the antiviral mechanism of the human MxA protein against influenza A and other RNA viruses. In the preceding funding period we solved the three dimensional structure of full-length MxA. It shows a composition of three domains; the globular G domain that binds and hydrolyzes GTP, the stalk that serves intermolecular interactions, and the central bundle signalling element that connects these two domains. This structural information combined with bioinformatics analysis of primate MxA proteins enabled us to identify a loop L4 that projects out of the compact structure of the MxA stalk domain as the target recognition site. In a further study we identified the nucleoprotein of influenza A virus as the main determinant of viral sensitivity towards the antiviral function of Mx proteins. These results will be the basis of our future projects aiming at understanding the molecular basis of the broad antiviral activity of MxA, characterizing the motif in the viral nucleoprotein of influenza A virus that determines Mx sensitivity, and identifying additional cellular factors that might be involved in MxA antiviral action. These insights might provide a scientific basis for the development of novel antiviral agents disturbing the function of viral nucleocapsids.

• DFG Programme: Research Grants