origin and phylogeography of dog rabies virus

1 Institut Pasteur, UPRE Lyssavirus Dynamics and Host Adaptation, World Health Organization Collaborating Centre for Reference and Research on Rabies, Institut Pasteur, 75724 Paris Cedex 15, France 2 Institut Pasteur of Cambodia, Phnom Penh, Cambodia 3 Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802, USA 4 Institut Pasteur of Ho Chi Minh City, Ho Chi Minh City, Vietnam 5 Wuhan Institute of Biological Products, Wuhan, Hubei Province 430060, PR China 6 Veterinary Research Department, Research Institute for Tropical Medicine, Ficc Alabang, Muntinlupa City 1781, Metro Manila, Philippines 7 Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA Correspondence Hervé Bourhy hbourhy{at}pasteur.fr 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. GenBank/EMBL/DDBJ accession numbers for the newly acquired N and G gene sequences are designated EU086128–EU086218. A supplementary figure and two supplementary tables are available with the online version of this paper.