Detail

Keywords

Foot-and-Mouth Disease Virus; Host-Pathogen Interactions; Protein Structure, Tertiary; Protein Synthesis Inhibitors; Rhinovirus; Vaccinia virus; West Nile virus

Research interests

Most viruses interfere with or modulate host systems to ensure successful replication. My group has been examining proteins from the common cold virus (rhinovirus), coxsackie virus,  foot-and-mouth disease virus (FMDV) and vaccinia virus. We have determined the structures of proteins from all of these viruses and investigated how they interact with cellular proteins to modify the physiology of the infected cell. For example,  proteinases of the common cold virus and FMDV cleave the the cellular protein called eukaryotic initiation factor 4G (eIF4G), a protein involved in recruiting capped cellular mRNA to the ribosomes. Cleavage during replication of the above mentioned viruses thus prevents capped cellular mRNA being translated. We also investigated how eIF4G interacts with a cellular partner by NMR. Viral protein synthesis is unaffected as it initiates internally downstream of the 5’ end of its RNA. With the vaccinia virus, we have determined the structure of a viral protein that modulates the host immune system and are using the structure to determine how the viral protein interacts with its cellular targets such as MyD88, a vital component of the signalling cascade involved in activating innate immunity.

Techniques, methods & infrastructure

• Biochemical and molecular techniques to express and purify recombinant proteins, especially proteinases.
• Protein structure determination with X-ray crystallography, NMR and SAXS.
• Measureing protein-protein interaction with SEC-MALLS, ITC, MST and NMR.
• Virological methods to measure viral replication and the effect of mutations thereon.
• Computer-predicted modelling of protein-protein interactions.

Grants

• Integrative Strukturbiologie (2015)
  Source of Funding: FWF (Austrian Science Fund), Doctoral Programs (DKs)
  Coordinator of the collaborative project
• Substrate recognition by picornaviral proteases L and 2A (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Structure and function of picornaviral proteases Lb and 2A (2011)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator

Selected publications

1. Fedosyuk, S. et al., 2014. Characterization and Structure of the Vaccinia Virus NF-κB Antagonist A46. Journal of Biological Chemistry, 289(6), pp.3749–3762. Available at: http://dx.doi.org/10.1074/jbc.M113.512756.
2. Steinberger, J. et al., 2014. Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage. Virology, 468-470, pp.397-408. Available at: http://dx.doi.org/10.1016/j.virol.2014.08.023.
3. Nikolay, B. et al., 2014. Validation of a structural comparison of the antigenic characteristics of Usutu virus and West Nile virus envelope proteins. Virus Research, 189, pp.87-91. Available at: http://dx.doi.org/10.1016/j.virusres.2014.05.018.
4. Fedosyuk, S. et al., 2016. Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins D. H. Fremont, ed. PLOS Pathogens, 12(12), p.e1006079. Available at: http://dx.doi.org/10.1371/journal.ppat.1006079.