The Global Phylogeography of Lyssaviruses - Challenging the 'Out of Africa' Hypothesis

Rabies virus kills tens of thousands of people globally each year, especially in resource-limited countries. Yet, there are genetically- and antigenically-related lyssaviruses, all capable of causing the disease rabies, circulating globally among bats without causing conspicuous disease outbreaks. The species richness and greater genetic diversity of African lyssaviruses, along with the lack of antibody cross-reactivity among them, has led to the hypothesis that Africa is the origin of lyssaviruses. This hypothesis was tested using a probabilistic phylogeographical approach. The nucleoprotein gene sequences from 153 representatives of 16 lyssavirus species, collected between 1956 and 2015, were used to develop a phylogenetic tree which incorporated relevant geographic and temporal data relating to the viruses. In addition, complete genome sequences from all 16 (putative) species were analysed. The most probable ancestral distribution for the internal nodes was inferred using three different approaches and was confirmed by analysis of complete genomes. These results support a Palearctic origin for lyssaviruses (posterior probability = 0.85), challenging the ‘out of Africa’ hypothesis, and suggest three independent transmission events to the Afrotropical region, representing the three phylogroups that form the three major lyssavirus clades.