title: Widespread Reassortment Shapes the Evolution and Epidemiology of Bluetongue Virus following European Invasion.
abstract: Genetic exchange by a process of genome-segment 'reassortment' represents an important mechanism for evolutionary change in all viruses with segmented genomes, yet in many cases a detailed understanding of its frequency and biological consequences is lacking. We provide a comprehensive assessment of reassortment in bluetongue virus (BTV), a globally important insect-borne pathogen of livestock, during recent outbreaks in Europe. Full-genome sequences were generated and analysed for over 150 isolates belonging to the different BTV serotypes that have emerged in the region over the last 5 decades. Based on this novel dataset we confirm that reassortment is a frequent process that plays an important and on-going role in evolution of the virus. We found evidence for reassortment in all ten segments without a significant bias towards any particular segment. However, we observed biases in the relative frequency at which particular segments were associated with each other during reassortment. This points to selective constraints possibly caused by functional relationships between individual proteins or genome segments and genome-wide epistatic interactions. Sites under positive selection were more likely to undergo amino acid changes in newly reassorted viruses, providing additional evidence for adaptive dynamics as a consequence of reassortment. We show that the live attenuated vaccines recently used in Europe have repeatedly reassorted with field strains, contributing to their genotypic, and potentially phenotypic, variability. The high degree of plasticity seen in the BTV genome in terms of segment origin suggests that current classification schemes that are based primarily on serotype, which is determined by only a single genome segment, are inadequate. Our work highlights the need for a better understanding of the mechanisms and epidemiological consequences of reassortment in BTV, as well as other segmented RNA viruses.
authors.affiliation: Vector-Borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, United Kingdom.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Nomikou
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hughes
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Wash
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Division of Infection and Immunity, Research Department of Infection, University College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.affiliation: French Agency for Food, Environment and Occupational Health and Safety (ANSES), Maisons-Alfort, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Breard
authors.affiliation: French Agency for Food, Environment and Occupational Health and Safety (ANSES), Maisons-Alfort, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Zientara
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Massimo
authors.initials: M
authors.lastname: Palmarini
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom; Institute of Biodiversity, Animal Health and Comparative Medicine, Boyd Orr Centre for Population and Ecosystem Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Biek
authors.affiliation: Vector-Borne Viral Diseases Programme, The Pirbright Institute, Pirbright, Woking, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Mertens
mesh_terms: D001819:Bluetongue / Q000453:epidemiology* / Q000235:genetics*; D001820:Bluetongue virus / Q000235:genetics*; D005060:Europe; D019143:Evolution, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D060888:Real-Time Polymerase Chain Reaction; D016865:Reassortant Viruses / Q000235:genetics*