TRANSLATING VIROLOGY INTO ECOLOGY: LINKING HOST AND VIRAL TRAITS TO VIRULENCE AND PATHOGEN EVOLUTION

Erin L. Keller

How and why pathogens harm their hosts are among the most important questions in biology. The host represents a pathogen’s environment—it relies on it for growth and reproduction—so harming the host seems, at first, counterproductive. Thus, there has been considerable theoretical and empirical work to understand what determines virulence and how it evolves. Most studies of virulence have been dominated by a single theory, the trade-off hypothesis, which posits that virulence may be an unavoidable cost of transmission. Yet, empirical support for this hypothesis has been equivocal, raising doubts about our assumptions of the determinants of virulence and consequently our ability to predict virulence in different contexts and how it evolves. This thesis is generally focused on the ecology and evolution of virulence, including investigating the underlying mechanisms driving virulence and broadly how it evolves using a diverse array of methods from in vitro to in vivo to in silico. I first provide a strong empirical test of one the most central and widely used assumptions in the literature, that, because pathogen replication necessarily exploits host resources, pathogen replication is positively related to virulence. I found that even in a system that should provide a best-case scenario for this relationship, this relationship was not observed and may not be as straightforward as assumed. I then considered an ecological perspective of virulence. While virulence is often assumed to be at least predominantly a pathogen trait, the actual level of damage to the host may be dominated by environmental factors such as temperature. I found that, in vivo, infection dynamics and outcomes were surprisingly similar among divergent viruses and that temperature played a strong role in determining the level of virulence, possibly through mediating viral replication rates. Collectively, these two studies find that virulence need not increase simply with pathogen replication, and highlights the need to consider environmental conditions in studies of virulence. Lastly, given that viral recombination can result in large changes in virulence and is recognized a major driver of virus evolution, I investigated the within-host conditions a de novo recombinant virus is likely to experience in its initial host and clarified what traits may promote the emergence of a de novo recombinant virus. Using an in silico approach, I found that strong advantages in replication-related traits were needed to overcome large numeric disadvantages. My results suggest that the initial transmission bottleneck may be the most important for de novo recombinants and that, aside from being exceedingly lucky, successful recombinants likely have clear advantages over their parents in replication. Depending on how replication relates to virulence in a particular system, advantages in these replication-related traits may favor the emergence of virulent recombinants. Taken together, this work highlights the utility in considering diverse perspectives of what causes virulence and how we expect it to evolve in different contexts. There are so many factors that govern the damage done to a host during infections it would be surprising if there were a single perspective or hypothesis that explained every or even most situations. Thus, studies of virulence would benefit from thinking more openly and critically about how empirical reality fits theory.

TRANSLATING VIROLOGY INTO ECOLOGY: LINKING HOST AND VIRAL TRAITS TO VIRULENCE AND PATHOGEN EVOLUTION

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