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

Oscar Morales Lezcano

I am Óscar and I come from Spain. I did my bachelor in Biochemistry and a master in Didactic Science in Seville university. Afterwards I did another master in Biomedicine in Granada university, whose internships allowed me to develop my interest in insect immunity: First, I studied the transcriptome of malaria mosquitoes infected by different species of Plasmodium and, second, I was involved in a project aimed at unravelling the interactome of non-structural proteins of dengue virus in mosquitoes.

This experience made me particularly curious about virus-host interactions and led me to start this new project in which I want to discover how Drosophila immune system influences RNA virus evolution. I would like to answer questions such as: how does host immunity influence virus infectivity and pathogenicity? What processes drive virus evolution in flies?

In addition, I would like to dig into molecular aspects of viral infection, looking for interactions between viral and host molecules that affect insect immunity and the fate of the infection.


Field:
Virology
Host institution:
Radboud University Medical Center (RadboudUMC), Netherlands
Local supervisor:
Prof. Dr. Ronald van Rij (RadboudUMC)
Local co-supervisor:
Prof. Dr. Martijn Huijnen (RadboudUMC)
Project partners:
Lara Fuhrmann (ESR 3)
Liuwei Wang (ESR 8)
Work packages:
WP 1.3 Virus-host interactions
WP 2.1 Microevolution: Virus quasispecies

Ronald van Rij
Martin Huijnen

Project description

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.