Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in Australia and New Zealand

ABSTRACTThe introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand during the 1990s as a means of controlling feral rabbits is an important case study in viral emergence. Both epidemics are exceptional in that the founder viruses share an origin and the timing of their release is known, providing a unique opportunity to compare the evolution of a single virus in distinct naive populations. We examined the evolution and spread of RHDV in Australia and New Zealand through a genome-wide evolutionary analysis, including data from 28 newly sequenced RHDV field isolates. Following the release of the Australian inoculum strain into New Zealand, no subsequent mixing of the populations occurred, with viruses from both countries forming distinct groups. Strikingly, the rate of evolution in the capsid gene was higher in the Australian viruses than in those from New Zealand, most likely due to the presence of transient deleterious mutations in the former. However, estimates of both substitution rates and population dynamics were strongly sample dependent, such that small changes in sample composition had an important impact on evolutionary parameters. Phylogeographic analysis revealed a clear spatial structure in the Australian RHDV strains, with a major division between those viruses from western and eastern states. Importantly, RHDV sequences from the state where the virus was first released, South Australia, had the greatest diversity and were diffuse throughout both geographic lineages, such that this region was likely a source population for the subsequent spread of the virus across the country.IMPORTANCEMost studies of viral emergence lack detailed knowledge about which strains were founders for the outbreak or when these events occurred. Hence, the human-mediated introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand from known starting stocks provides a unique opportunity to understand viral evolution and emergence. Within Australia, we revealed a major phylogenetic division between viruses sampled from the east and west of the country, with both regions likely seeded by viruses from South Australia. Despite their common origins, marked differences in evolutionary rates were observed between the Australian and New Zealand RHDV, which led to conflicting conclusions about population growth rates. An analysis of mutational patterns suggested that evolutionary rates have been elevated in the Australian viruses, at least in part due to the presence of low-fitness (deleterious) variants that have yet to be selectively purged.