PS 44-105 - ´╗┐The effect of disease dynamics on viral evolutionary rates: A modeling study to consider ecological determinants of substitution rate variation in chikungunya virus

Wednesday, August 10, 2011
Exhibit Hall 3, Austin Convention Center
Stacy O. Scholle and Katia Koelle, Biology, Duke University, Durham, NC

The evolutionary rates of RNA viruses can differ from one another by several orders of magnitude (Jenkins et. al, J Mol Evol. 2002). Much of this variation has been explained by differences in these viruses’ mutation rates and by differences in their selective environments. However, substitution rate variation has also been observed in a single RNA virus when genetic variation is thought to be phenotypically neutral. This pattern is much more difficult to explain, and we address this phenomenon here in the context of chikungunya virus (CHIKV). Previous work has shown that different lineages of CHIKV have different evolutionary rates (Volk et. al, J Virology 2010). This work suggested that enzootic and endemic disease dynamics result in slower evolutionary rates than urban epidemic dynamics. To evaluate the feasibility of this hypothesis, we designed a model framework that allows us to determine how substitution rates change with either endemic or epidemic dynamics. The model keeps track of the number of viral replication cycles that accumulate via mosquito and human infection over time.


Simulating this model under endemic conditions, we find that the mean number of viral replication cycles increases linearly over time, indicating a constant evolutionary rate. Simulations with epidemic dynamics result in evolutionary rates more rapid than endemic dynamics until just after the epidemic peak. This is followed by a rapid decrease in evolutionary rates that are slower than those simulated with endemic dynamics. However, the total number of replication cycles over the time-scale of an epidemic does not differ between endemic and epidemic simulations. These results indicate that endemic versus epidemic dynamics have transient but not long-term effects on the rates of neutral evolution.

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