Illuminating coronavirus-host interactions

Abstract

Viruses are infectious agents incapable of growing or reproducing outside a host cell. They are completely dependent on the cellular machinery of the host for their multiplication. On the other hand, however, viruses also have to deal with the immune defences of the host. Apparently, viruses are walking a thin line between hijacking the cellular machinery of the host and at the same time escaping from its defences. Coronaviruses (CoVs), just like any other virus, interact at multiple levels with their host: at the cellular level, as they exploit the cellular machinery for their own propagation, as well as at the level of the organism by manipulating/evading host immune responses. Although a lot is known about the molecular biology of CoVs, our knowledge about these CoV-host interactions is still rudimentary. The aim of this thesis was to gain further insight into these interactions, both at the molecular/cellular level and at the level of the organism, the host. In chapter 2 we describe an improved microarray protocol for whole-genome gene expression profiling of virus-infected cells, which allowed us to subsequently study the reaction of the cell’s transcriptome to CoV infection, as described in chapter 3. In chapter 4, 5 and 6 the involvement of several host cellular pathways/proteins in the replication of MHV in cell culture is described in detail. In chapter 7, bioluminescence imaging was used as a new tool for studying several aspects of CoV-host interactions in living mice. Chapter 8 describes the whole-genome gene expression profiling of mice of different genetic backgrounds, providing more insight into type I IFN-independent and -dependent transcriptional responses after infection with MHV.