Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Modelling HIV virulence evolution in the context of immune escape
Christiaan H. van Dorp, Rob J. de Boer, Michiel van Boven

Last modified: 2014-06-09

Abstract


A pathogen like HIV evolves rapidly under multiple levels of selection, and has to cope with a heterogeneous host population. Although these aspects have been studied before, the true nature of host-heterogeneity has not been addressed to our satisfaction. During (untreated) infection, HIV evades cellular immune responses and because of the massive polymorphism of the Human Leukocyte Antigen, the targets of these responses (epitopes) differ strongly between hosts.

 

Supported by data, it has been suggested that HIV has evolved virulence levels that are optimal for transmission. Some models indeed predict this, but others caution that this mode of adaptation is not self-evident, mostly due to the short-sightedness of evolution during the infection of an individual host. Several theories have been proposed to better explain the evolution of virulence, and we aim to contribute to these attempts.

 

We are developing a model of HIV's evolutionary dynamics that is highly detailed and realistic, and captures the interesting features of host-heterogeneity, immune escape and compensatory mutations, and selection on multiple levels. We hypothesise that these properties might be sufficient to explain HIV's observed virulence distribution.