Detail

Keywords

Binding Sites, Antibody; Flavivirus

Research interests

My group studies specific aspects of the molecular biology and immunology of orthoflaviviruses. These viruses have a worldwide impact as human disease agents and include tick-borne encephalitis virus and the mosquito-borne dengue, Zika, yellow fever, Japanese encephalitis, and West Nile viruses. Orthoflaviviruses are small enveloped viruses with an icosahedral surface structure. The most prominent protein component of the viral envelope is the E protein, which mediates cell entry and is therefore the primary target for neutralizing antibodies. Our research aims to provide new structural and functional insights into the life cycle and the molecular details of the antigenic structure of orthoflaviviruses. We place a strong focus on the structure-based investigation of the balance between neutralizing and infection-enhancing effects of antibodies. This work could thus influence vaccine design as well as the development of antiviral agents and diagnostic antigens.

These studies are funded by the Austrian Science Fund FWF (Grant no. PAT5925724; https://www.fwf.ac.at/forschungsradar/10.55776/PAT5925724) and the European Union (Grant Agreement No. 101191725; https://inflame-horizon.eu/).

Techniques, methods & infrastructure

„State of the art“ basic molecular biology and virology techniques, pro- and eukaryotic expression systems, protein chemical analyses, cell culture techniques, immunological assays for the analysis of antigens and antibodies, viral mutagenesis systems, in vitro assays for viral functions

Selected publications

1. Medits, I. et al., 2020. Extensive flavivirus E trimer breathing accompanies stem zippering of the post‐fusion hairpin. EMBO reports, 21(8). Available at: http://dx.doi.org/10.15252/embr.202050069.
2. Malafa, S. et al., 2020. Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans D. J. Gubler, ed. PLOS Neglected Tropical Diseases, 14(2), p.e0008034. Available at: http://dx.doi.org/10.1371/journal.pntd.0008034.
3. Vaney, M.-C. et al. (2022) ‘Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery’, Nature Communications, 13(1). Available at: https://doi.org/10.1038/s41467-022-31111-y.
4. Roßbacher, L. et al. (2023) ‘Effect of previous heterologous flavivirus vaccinations on human antibody responses in tick‐borne encephalitis and dengue virus infections’, Journal of Medical Virology, 95(11). Available at: https://doi.org/10.1002/jmv.29245.
5. Stiasny, K. et al. (2022) ‘Impact of structural dynamics on biological functions of flaviviruses’, The FEBS Journal, 290(8), pp. 1973–1985. Available at: https://doi.org/10.1111/febs.16419.