Virus evolution

RNA viruses have high mutation rates and short generation times and they often exist in large populations. These characteristics result in extreme evolutionary dynamics producing genetically diverse populations called quasispecies. Evolutionary changes in RNA viruses can be observed on very short time scales of weeks to months. For this reason, they are referred to as measurably evolving populations and they are attractive model systems for developing and testing evolutionary models and theories.

We are specifically interested in viral competition. A population of foot-and-mouth disease virus had been observed to diversify into two genetically distinct subpopulations, one more effective in producing offspring in co-infected cells, the other capable of faster cell killing. We have analyzed the consequences of this competition-colonization trade-off using mathematical modeling and predicted density-dependent selection. This prediction was confirmed experimentally: competitors outcompete colonizers under high multiplicities of infection and vice versa.

The ODE model of two competing virus types in cell culture was extended to multiple types and constant supply of uninfected cells to closer resemble the in vivo situation. The generalized ODE and PDE models predict that a viral quasispecies that displays a dense spectrum of cell killing rates will evolve into a population of coexisting variants dominated by less virulent competitors. Thus, the competition-colonization trade-off provides a mechanism for the attenuation of viruses.

Selected references

• Ojosnegros S, Beerenwinkel N, Antal T, Nowak MA, Escarmís C, Domingo E (2010). Competition-colonization dynamics in an RNA virus. Proceedings of the National Academy of Sciences U. S. A., 107(5):2108–2112.
• Delgado-Eckert E, Ojosnegros S, Beerenwinkel N (submitted). The evolution of virulence in RNA viruses under a competition-colonization trade-off. arXiv:1001.3101v1