title: Spatio-temporal Analysis of the Genetic Diversity of Arctic Rabies Viruses and Their Reservoir Hosts in Greenland.
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.
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Diagnostic Virology, Greifswald-Insel Riems, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hanke
authors.affiliation: FLI, Institute of Molecular Virology and Cell Biology, Greifswald-Insel Riems, Germany.
authors.forename: Conrad M
authors.initials: CM
authors.lastname: Freuling
authors.affiliation: FLI, Institute of Epidemiology, Greifswald-Insel Riems, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Department of Veterinary Medicine, University of Alaska, Fairbanks, Alaska, United States of America.
authors.forename: Karsten
authors.initials: K
authors.lastname: Hueffer
authors.affiliation: Institute of Arctic Biology, University of Alaska, Fairbanks, Alaska, United States of America.
authors.forename: Kris
authors.initials: K
authors.lastname: Hundertmark
authors.affiliation: Animal Health Microbiology Research, Canadian Food Inspection Agency (CFIA), Centre of Expertise for Rabies, Ottawa Laboratory, Ottawa, Ontario, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Nadin-Davis
authors.affiliation: Animal and Plant Health Agency (APHA), Wildlife Zoonoses and Vector-borne Diseases Research Group, Addlestone, Surrey, United Kingdom.
authors.forename: Denise
authors.initials: D
authors.lastname: Marston
authors.affiliation: Animal and Plant Health Agency (APHA), Wildlife Zoonoses and Vector-borne Diseases Research Group, Addlestone, Surrey, United Kingdom.|University of Liverpool, Department of Clinical Infection, Microbiology and Immunology, Liverpool, United Kingdom.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fooks
authors.affiliation: DTU National Veterinary Institute, Technical University of Denmark, Lindholm, Kalvehave, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Bøtner
authors.affiliation: FLI, Institute of Molecular Virology and Cell Biology, Greifswald-Insel Riems, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Diagnostic Virology, Greifswald-Insel Riems, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beer
authors.affiliation: DTU National Veterinary Institute, Technical University of Denmark, Lindholm, Kalvehave, Denmark.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Rasmussen
authors.affiliation: FLI, Institute of Molecular Virology and Cell Biology, Greifswald-Insel Riems, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Müller
authors.affiliation: Friedrich-Loeffler-Institut (FLI), Institute of Diagnostic Virology, Greifswald-Insel Riems, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Höper
mesh_terms: D000818:Animals; D000835:Animals, Wild / Q000821:virology; D001110:Arctic Regions; D004197:Disease Reservoirs / Q000821:virology*; D005589:Foxes / Q000821:virology*; D014644:Genetic Variation; D016679:Genome, Viral; D006116:Greenland; D010802:Phylogeny; D011818:Rabies / Q000662:veterinary* / Q000821:virology; D011820:Rabies virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*