PhD Projects » ESR 9: Impact of host immune pathways on virus evolution

Field:Virology
Host institution:Radboud University Medical Center (RadboudUMC), Netherlands
Local supervisor: Prof. Dr. Ronald van Rij (RadboudUMC, Dept. Medical Microbiology, Radboud Institute for Molecular Life Sciences)
Local co-supervisor: Prof. Dr. Martijn Huijnen (RadboudUMC, Centre for Molecular and Biomolecular Informatics)
Project partner: ESR 3, ESR 8

Evolution of viruses is strongly affected by antagonistic co-evolution of virus and host. Host immune pathways select for viruses that evade or suppress the immune response, which in turn may drive counter-adaptations in host immune genes. For example, the main antiviral system of insects (RNA interference, RNAi) is actively suppressed by many insect viruses, which likely induces rapid evolution of RNAi genes of the host, as has been observed in the model organism Drosophila melanogaster (fruit fly). Life history theory predicts that there may be trade-offs that prevent simultaneous improvements in fitness traits, such as resistance to pathogens and virulence. The overall aim of ESR 9 is to understand the effect of host antiviral responses on viral population dynamics.

The main objectives are

  • to study virus evolution and quasispecies composition under experimental evolution in a natural virus-host system under conditions in which the host immune system is functional or inactivated;
  • to isolate virus population to study the evolution of virus phenotypes such as virus replication and pathogenicity under experimental evolution.

For these studies, we will use natural Drosophila viruses, such as Nora virus, a wide-spread pathogen of the fruit fly Drosophila melanogaster that is transmitted via the fecal-oral route and encodes a suppressor of the antiviral RNAi response. Nora virus will be serially passaged over wildtype flies as well as immune defective flies. Evolution of viral sequences will be studied over time and virus populations will be isolated in parallel and analyzed for phenotypes such as viral loads and host survival, and specific readouts of virus-induced pathology and suppression of RNAi. Viral population structures will be analyzed in collaboration with ESR 3 and ESR 8 to develop methods to identify evolving and co-evolving sites and epistatic interactions across viral genomes.