PhD defence S.E. (Shirley) Braspenning

Dissertation in short:

My research has focused on varicella-zoster virus (VZV), a herpesvirus that causes both chickenpox during childhood and shingles later in life. Between these two episodes of disease, the virus persists in a sleep-like state in the nerves called latency. During latency, the virus is silent and no new viral particles are produced. While chickenpox is usually a mild disease, shingles is associated with many complications for which no appropriate treatment exists. It is therefore important to learn how the virus replicates and how it establishes and maintains latency. This knowledge will ultimately lead to the development of new drugs that can remove the latent virus or prevent shingles from occurring.  

In this thesis, I describe the discovery of a new viral gene (called VLT) that is specifically expressed during latency, and might be involved in keeping the virus silent. We used CRISPR/Cas9 to remove this protein from the virus and showed that without VLT the virus grows slower, but can still replicate. Next, we studied the protein interactions that VLT has to discover a potential function for the protein. 

In the second part of my thesis, we used state-of-the-art sequencing techniques to unravel the complexity of gene expression of Varicelloviruses during lytic infection. Importantly, we defined in which order the virus expresses its genes, crucial to understanding the life cycle of the virus. We further analyzed how gene expression is conserved between two closely related herpesviruses.