The origin and phylogeography of dog rabies virus

Abstract

Rabies is a progressively fatal and incurable viral encephalitis caused by a lyssavirus infection. Almost all of the 55 000 annual rabies deaths in humans result from infection with dog rabies viruses (RABV). Despite the importance of rabies for human health, little is known about the spread of RABV in dog populations, and patterns of biodiversity have only been studied in limited geographical space. To address these questions on a global scale, we sequenced 62 new isolates and performed an extensive comparative analysis of RABV gene sequence data, representing 192 isolates sampled from 55 countries. From this, we identified six clades of RABV in non-flying mammals, each of which has a distinct geographical distribution, most likely reflecting major physical barriers to gene flow. Indeed, a detailed analysis of phylogeographic structure revealed only limited viral movement among geographical localities. Using Bayesian coalescent methods we also reveal that the sampled lineages of canid RABV derive from a common ancestor that originated within the past 1500 years. Additionally, we found no evidence for either positive selection or widespread population bottlenecks during the global expansion of canid RABV. Overall, our study reveals that the stochastic processes of genetic drift and population subdivision are the most important factors shaping the global phylogeography of canid RABV.

Fig. 1

ML phylogeny of 151 sequences from the N-coding region of RABV. The estimated TMRCA for this sample of viral lineages, as well as its 95 % HPD values, are indicated. The major clades of RABV are also indicated, denoted by squares at the relevant nodes. Branches are colour-coded by species group: black, dogs; red, bats; blue, alternative reservoir hosts (such as the red fox); green, spill-over hosts (such as humans, bovines, wolf). Horizontal branches are drawn to a scale of nucleotide substitutions per site, with bootstrap support values (>90 % and 73 % for the Indian subcontinent clade) shown for key nodes.

Fig. 2

ML phylogeny of 74 sequences from the complete G-coding region of RABV. The estimated TMRCA for this sample of viral lineages, as well as its 95 % HPD values, are indicated. The major clades of RABV are also indicated, denoted by squares at the relevant nodes. Branches are coloured-coded in the same manner as Fig. 1. Horizontal branches are drawn to scale, with bootstrap support values (>90 %) shown for key nodes.