Molecular basis of high influenza A virus susceptibility in Mus musculus castaneus carrying apparently intact Mx genes

• Applicant: Professor Dr. Peter Stäheli
• Subject Area: Virology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 249167911

• Final Report Year: 2018

Final Report Abstract

This project helped increasing our knowledge on the functional consequences of sequence variations in the MX1 protein of different Mus species. It showed that some MX1 variants acquired mutations that either reduce the metabolic stability of the mature protein or lower the binding affinity of MX1 for its viral target. This work forms a solid basis for future studies aimed at understanding why evolution select for MX1 variants with reduced activity in some murine species. At present this important question remains entirely unresolved.

Publications

• Functional comparison of Mx1 from two different mouse species reveals the involvement of loop L4 in the antiviral activity against influenza A viruses. J. Virol. 89: 10879-10890 (2015)
  Verhelst, J., Spitaels, J., Nürnberger, C., De Vlieger, D., Ysenbaert, T., Staeheli, P., Fiers, W., & X. Saelens
  (See online at https://doi.org/10.1128/JVI.01744-15)
• (2016). Influenza virus susceptibility of wild-derived CAST/EiJ mice is determined by mutations in the Mx1 resistance gene. Doktorarbeit Fakultät für Biologie, Universität Freiburg
  Nürnberger, C.
  
• Influenza virus susceptibility of wildderived CAST/EiJ mice results from two amino acid changes in the MX1 restriction factor. J. Virol. 90: 10682-10692 (2016)
  Nürnberger, C., Zimmermann, V., Gerhardt, M., & P. Staeheli
  (See online at https://doi.org/10.1128/JVI.01213-16)