Abstract
An extensive body of theory addresses the topic of pathogen virulence evolution, yet few studies have empirically demonstrated the presence of fitness trade-offs that would select for intermediate virulence. Here we show the presence of transmission-clearance trade-offs in dengue virus using viremia measurements. By fitting a within-host model to these data, we further find that the interaction between dengue and the host immune response can account for the observed trade-offs. Finally, we consider dengue virulence evolution when selection acts on the virus’s production rate. By combining within-host model simulations with empirical findings on how host viral load affects human-to-mosquito transmission success, we show that the virus’s transmission potential is maximized at production rates associated with intermediate virulence and that the optimal production rate critically depends on dengue’s epidemiological context. These results indicate that long-term changes in dengue’s global distribution impact the invasion and spread of virulent dengue virus genotypes.
Highlights
An extensive body of theory addresses the topic of pathogen virulence evolution, yet few studies have empirically demonstrated the presence of fitness trade-offs that would select for intermediate virulence
Using a withinhost model fit to viremia measurements from symptomatic dengue-infected individuals, we found that this trade-off can be explained by the interaction of the virus with the host immune response, providing empirical support for this hypothesis from theoretical studies[10,21]
We considered whether a transmission-clearance trade-off analogous to the trade-off we observed empirically could result in selection pressures on dengue virus to evolve to intermediate virulence
Summary
An extensive body of theory addresses the topic of pathogen virulence evolution, yet few studies have empirically demonstrated the presence of fitness trade-offs that would select for intermediate virulence. By combining within-host model simulations with empirical findings on how host viral load affects human-to-mosquito transmission success, we show that the virus’s transmission potential is maximized at production rates associated with intermediate virulence and that the optimal production rate critically depends on dengue’s epidemiological context These results indicate that long-term changes in dengue’s global distribution impact the invasion and spread of virulent dengue virus genotypes. Virulence can be defined as the ability of a pathogen to cause disease[7] In this case, evolution towards intermediate virulence can result from trade-offs in many different fitness components[8], rather than only through the classical trade-off between transmission and disease-induced host mortality. By fitting an existing within-host dengue model to the observed viremia measurements, we show that this observed trade-off can be explained by the interaction of the virus with the host immune response, consistent with recent arguments that the host immune response can be an important factor limiting the evolution of higher transmission rates[10,21]
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