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Understanding pathogen selection pressures at the within- and between-host levels

University of British Columbia

Many infectious pathogens, and in particular viruses, have an extremely high rate of mutation. This can lead to rapid evolution driven by selection pressures operating at both the within- and between-host levels, as strains compete for resources within their chosen host while also competing to effectively transmit to new hosts. In the case of chronic viral infections, such as the human immunodeficiency virus (HIV) or hepatitis C, substantial viral evolution may take place within a single infected host. The fitness of a pathogen has been studied at the between-host level and at the within-host level, but linking the two levels of selection pressure is a difficult problem that has yet to be studied satisfactorily. We modify a simple model describing the within host dynamics of HIV infection by including multiple pathogen strains with different properties and allowing these strains to mutate. Within the host we observe different strategies for pathogen success during different stages of infection, which often leads to different strains predominating within the host over the course of infection. We then embed our within-host model into a Monte Carlo simulation that models the interactions between infected individuals. This approach allows us to combine selective pressure at the within-host level with pressures at the between-host level and helps us to predict which strains are most likely to be present within the population. We show that under our model assumptions the co-existence of multiple strains is possible and we explore the factors leading to the success of a pathogen.

Text

2010-01-08

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http://hdl.handle.net/2429/17871

Mathematics

University of British Columbia

UBCV

DSpace