PhD defence Y.J. (Jurre) Siegers

Dissertation in short:

Influenza virus infections are a major cause of respiratory tract disease in humans. Each year, seasonal influenza epidemics infect about 5-10% of adults and 20-30% of children globally
with ~1 billion cases, 3-5 million hospitalizations, and 290-650 thousand deaths [1, 2]. The most common and under-recognized extra-respiratory complications of influenza are central
nervous system (CNS) and cardiac diseases [3]. The frequency and severity of influenza virus associated CNS disease differs between subtypes and strains [3, 4]. Highly pathogenic
avian influenza (HPAI) H5N1 virus infections [5-8] are more often associated with extrarespiratory disease than seasonal H3N2 or 2009 pandemic H1N1 influenza viruses [9]. So far, it is poorly understood which viral factors are important for the ability to spread to, replicate in, and spread throughout extra-respiratory tissues, including the CNS. In this thesis, I studied the ability of different pandemic and zoonotic influenza viruses to spread & cause disease outside the respiratory tract, with a focus on the CNS and cardiovascular system (chapter 2, chapter 3, and chapter 6). In addition, I studied the effect of diet induced obesity on extra-respiratory disease of 2009 H1N1 influenza virus infections (chapter 3). To get more insight into viral factors important for efficient replication inside the CNS, I studied the ability of different influenza viruses to replicate in cells of the CNS, chapter 4, chapter 5. Finally, in chapter 6, I evaluated whether vaccination or antivirals could prevent or reduce influenza virus to spread outside the respiratory tract.