Abstract
There has been limited knowledge on spatio-temporal epidemiology of zoonotic arctic fox rabies among countries bordering the Arctic, in particular Greenland. Previous molecular epidemiological studies have suggested the occurrence of one particular arctic rabies virus (RABV) lineage (arctic-3), but have been limited by a low number of available samples preventing in-depth high resolution phylogenetic analysis of RABVs at that time. However, an improved knowledge of the evolution, at a molecular level, of the circulating RABVs and a better understanding of the historical perspective of the disease in Greenland is necessary for better direct control measures on the island. These issues have been addressed by investigating the spatio-temporal genetic diversity of arctic RABVs and their reservoir host, the arctic fox, in Greenland using both full and partial genome sequences. Using a unique set of 79 arctic RABV full genome sequences from Greenland, Canada, USA (Alaska) and Russia obtained between 1977 and 2014, a description of the historic context in relation to the genetic diversity of currently circulating RABV in Greenland and neighboring Canadian Northern territories has been provided. The phylogenetic analysis confirmed delineation into four major arctic RABV lineages (arctic 1–4) with viruses from Greenland exclusively grouping into the circumpolar arctic-3 lineage. High resolution analysis enabled distinction of seven geographically distinct subclades (3.I – 3.VII) with two subclades containing viruses from both Greenland and Canada. By combining analysis of full length RABV genome sequences and host derived sequences encoding mitochondrial proteins obtained simultaneously from brain tissues of 49 arctic foxes, the interaction of viruses and their hosts was explored in detail. Such an approach can serve as a blueprint for analysis of infectious disease dynamics and virus-host interdependencies. The results showed a fine-scale spatial population structure in Greenland arctic foxes based on mitochondrial sequences, but provided no evidence for independent isolated evolutionary development of RABV in different arctic fox lineages. These data are invaluable to support future initiatives for arctic fox rabies control and elimination in Greenland.
Highlights
Rabies, an ancient disease known for millennia, is caused by lyssaviruses of the Rhabdoviridae family [1]
The results reveal the existence of a single arctic rabies virus (RABV) lineage in Greenland, which has evolved into multiple distinct variants
To enable in-depth phylogenetic analysis, viral sequences encoding all genes were generated for all arctic RABV samples (S1 Table, Fig 1)
Summary
An ancient disease known for millennia, is caused by lyssaviruses of the Rhabdoviridae family [1]. The prototypical rabies virus (RABV) has a global distribution and the domestic dog is the host reservoir responsible for the vast majority of the estimated 60,000 human rabies cases annually [2]. Other RABV host reservoirs in terrestrial wildlife are primarily meso-carnivores. Arctic foxes have considerably variable home ranges (5–120 km2) than any other meso-carnivore RABV reservoir host [6–8] and can roam over large areas and migrate over extremely long distances [4,8]. From an epidemiological point of view, this may be an important factor for the spread of RABV in northern Polar regions where rabies-like diseases have been described for about 150 years [9], among sledge dogs in Greenland as early as 1859. Confirmation of the existence of rabies in Greenland was only provided 100 years later, when Jenkins and Wamberg [10] demonstrated the presence of RABV in dogs and arctic foxes. A recent epidemiological study of arctic fox rabies in Greenland between 1969 and 2011 revealed that the disease flared up every 5–10 years on average, whereby most rabid foxes were reported from southern Greenland [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
