The Molecular And Evolutionary Determinants Of Hostswitching Viruses
Emerging infectious diseases represent imminent threats to human and animal health worldwide and can impose immense economic burdens, particularly on the world's most impoverished regions. Cross-species transmission of pathogens represents a common path towards disease emergence, but the mechanisms that lead to successful host jumping are incompletely understood. Here I have addressed some of the pathogen-associated factors involved in successful host jumping and have analyzed the evolutionary dynamics of the novel pathogen in the new host after cross-species transfer. These studies were performed using two emerging diseases of dogs: Canine Parvovirus (CPV) and Canine Influenza virus (CIV). While CPV emerged in the mid-1970s from an endemic virus of cats and has since become endemic in the global dog population, CIV was first described as a pathogen of dogs in 2004 - thus representing a new, likely not completely hostadapted virus. Contrasting the evolutionary dynamics of these two pathogens which share the same host species allowed a powerful analysis of the determinants and risk factors for disease emergence. In particular, I focused these studies on understanding the viral population dynamics in infected animals - contrasting where applicable the dynamics in the novel and the ancesteral host species, and dissecting host-associated effects and the impact of cross-immunity. For the case of CPV, I further analyzed the evolutionary dynamics of the novel virus on a population level since its emergence contrasting those to the dynamics observed in the ancesteral virus. Finally, I analyzed the effect of potentially host-specific codon usage and codon usage bias for the evolution of CPV. Because CpG methylation might represent an important driver of codon bias in the CPV genome, some work was dedicated to obtain a more comprehensive understanding of this major driver in DNA virus evolution. The results presented here show similarities but also marked differences between the evolutionary dynamics of CPV and CIV, and between the novel and ancesteral viruses. Further research is needed but it appears that key drivers differ between pathogens and between time intervals after emergence. However, some common mechanisms appear to be shared between viruses and others appear conserved between hosts.
dissertation or thesis