Molecular phylogenetics of the lyssaviruses--insights from a coalescent approach.

Technical improvements over the past 2 decades have enormously facilitated the generation of nucleotide sequence data for lyssavirus collections. These databases are amenable to methods of phylogenetic analysis, which attempt to define the taxonomic structure of this genus and predict the evolutionary relationships of current circulating strains. Coupled with a range of mathematical tools to explore the appropriateness of nucleotide substitution models and test for positive selection, the evolutionary process is being explored in detail. Despite the potential for high viral mutation levels, the operation of purifying selection appears to effectively constrain lyssavirus evolution. The recent development of coalescent theory has provided additional approaches to data analysis whereby the time frame of emergence of viral lineages can be most reliably estimated. Such studies suggest that all currently circulating rabies viruses have emerged within the past 1500 years. Moreover, through the capability of analyzing viral population dynamics and determining patterns of population size variation, coalescent approaches can provide insight into the demographics of viral outbreaks. Whereas human-assisted movement of reservoir host species has clearly facilitated transfer of rabies between continents, topographical landscape features significantly influence the rate and extent of contiguous disease spread. Together with empirical studies on virus diversity, the application of coalescent approaches will help to better understand lyssavirus emergence, evolution, and spread. In particular, such methods are presently facilitating exploration of the factors operating to limit the ability of lyssaviruses to establish new persistent virus-host associations and ultimately control the emergence of new species of this genus.