Viruses circulate predominantly in their natural reservoir host but frequently also infect other species. However, to establish a new lineage the virus has to adapt to the new environment by acquiring advantageous new mutations. These mutations also influence the secondary structure of the viral DNA and RNA, in turn affecting the replication process. ESR 8 will study the fundamental correlation between virus evolution and RNA secondary structures.
Being more specific, in case of segmented genomes (e.g. influenza A virus (IAV)) packaging is influenced by the secondary structure of the virus genomic RNA segments. In cells co-infected with different viruses, new variants with mixed genomes can emerge that have the potential to overcome the natural host species barrier and to cause a devastating pandemic. Mixing of viral segments, also designated genetic reassortment, is possible due to very efficient incorporation of different genome segments into one virus particle.
ESR 2 will systematically generate reassortant viruses between two human IAVs and select those that replicate most efficiently for further functional studies. Additionally, ESR 2 will use chemical probing to compare the genome structure in parental and those reassortant viruses. ESR 1 will study genetic reassortment events of IAV and especially the role of RNA-RNA interaction that is supposed to coordinate the interaction of the different genomes which are finally incorporated into viral particles. The focus of ESR 1 is to develop a computational tool that can predict the complex interplay of the RNA-RNA interaction required for genome packing between quite diverse IAV based on experimental data.