PhD Defence: Visualizing single-cell dynamics of picornavirus replication and virus-host interactions

Summary of dissertation

The picornaviruses are a large group of diverse RNA viruses that infect both humans and animals. The most well-known example is poliovirus, which is the cause of debilitating paralytic poliomyelitis, but the family also includes other consequential human and animal pathogens such as coxsackieviruses, echoviruses, numbered enteroviruses (e.g., EV-A71 and EV-D68), foot-and-mouth disease virus, rhinoviruses and cardioviruses. 

To rationally design new and effective antiviral drugs, it is essential to understand how these viruses infect and modify their target cells, how they replicate their genomes and how they interact with the cellular antiviral defense pathways, especially during the earliest phases of infection, when the outcome of infection is still being decided. However, it is very difficult using conventional experimental approaches to achieve high enough sensitivity or resolution to capture many of the events related to early infection. Moreover, to look at dynamic processes requires live-cell measurements. 

In my PhD work we set out to overcome these challenges to study early picornavirus infection and antiviral response dynamics. We established several microscopy assays that can visualize picornavirus infection and the cellular antiviral response in individual cells with single-molecule sensitivity in real-time. Next, we used these microscopy assays in combination with advanced virology techniques to study the role of individual viral proteins and to examine changes in membrane organization during picornavirus infection, and how these processes underly viral evasion of antiviral defense mechanisms.

The ceremony will begin with a short layman’s talk. The livestream will therefore start fifteen minutes earlier.