The recent coronavirus pandemic vividly demonstrated the importance of virus research; not only must we understand viruses’ functioning to fight emerging threats but viruses are also useful model systems for the interpretation of complex cellular processes. Being dependent on the host cell for their multiplication, viruses developed diverse strategies to usurp the cellular synthetic machinery for their own benefit. We decided to work on the comparably harmless and simple common cold viruses that belong to the large picornavirus family. Our findings could thus occasionally be extrapolated to more serious human and animal pathogens belonging to the same family.
The common cold usually remains limited to the nasal mucosa, as indicated in the name ‘rhinoviruses (RVs)’. Numerous students were involved in working out how RVs specifically bind to the target cells, which pathways they exploit for gaining access to the cell and how they release their RNA genome for infection. From the released viral RNA ribosomes produce tiny amounts of a viral proteinase that specifically shuts down the synthesis of cellular proteins and exclusively viral proteins are being made. Although tiny, of simple architecture and with a small RNA genome, RVs still leave us open questions to be addressed. My students collaborated with specialists in fields including Structural Biology, Analytical Chemistry, and Biophysics, to just name a few. Work with viruses thus conveys profound general knowledge and training in diverse techniques. Noteworthy, my students came from numerous different countries enriching the mutual understanding of cultures and societies.
Electron microscopy and X-ray crystallography has shown that the attachment points of the viral genomic RNA to the inner wall of the protein shell change on expansion of the particle in vitro. To find out whether the same happens in vivo we shall isolate intermediates of the process from cells shortly after infection and analyse their 3D-structure by cryo-electron microscopy image reconstruction. As we already saw particles lacking a pentamer in negative stain we shall attempt isolating and analysing such particles from infected cells. In parallel, we shall compare the secondary structure of the RNA inside the virion, in the expanded particle, and in refolded RNA by selective chemical modification followed by deep sequencing. Finally, we shall explore the possibility to inhibit RNA exit with compounds binding defined structural elements of the RNA; such compounds might be useful as novel antivirals.
Doctorate at the Université Montpellier, France, Venia Legendi at the Medical Faculty, University of Vienna (Biochemistry), Fellowship of the French Governement, Fellowship of the Ligue Française de la Lutte contre le Cancer, Höchst Preis, Th. Körner Preis, sabbatical in Structural Biology at the IBMB-CSIC, Barcelona, Spain, 176 peer reviewed publications in scientific journals.