Genetic reassortment between divergent IAVs in the host is a highly biased process in which only a small fraction of all possible genotypes are efficiently produced. This restriction is due to the limited compatibility between packaging signals of divergent IAVs and the limited conservation of RNA-RNA interactions required for genome packaging, but might also be influenced by the host as environment. Thus, analyses of genetic reassortment not only shed light on how viruses with pandemic potential are produced, but also provides crucial information about the coordinated incorporation of the segmented IAV genome.
Therefore, we will:
- Systematically generate reassortants between two human IAVs that will contain seven segments from a parental H1N1 virus and one segment from a parental H3N2 virus.
- Compare the secondary structure of the genomic RNA segments in the two parental and up to eight selected reassortant viruses grown in human cells using chemical probing (SHAPE-MAP). This analysis will be performed with ESR 4 and highlights differences in RNA-RNA interactions between parental and reassortant viruses. These experimental data will be used by ESR 1 to predict packaging signals.
- We will next experimentally verify ESR 1 packaging predictions.
- Finally, we will generate antivirally active biochemical substances that specifically interfere with RNA-RNA interactions between genomes, such as locked nucleic acids (LNA).
Doctorate will be awarded at University of Strasbourg.