RT Journal Article SR Electronic T1 Evolutionary stasis of an RNA virus indicates arbovirus re-emergence triggered by accidental release JF bioRxiv FD Cold Spring Harbor Laboratory SP 2019.12.11.872705 DO 10.1101/2019.12.11.872705 A1 David J Pascall A1 Kyriaki Nomikou A1 Emmanuel Bréard A1 Stephan Zientara A1 Ana da Silva Filipe A1 Bernd Hoffmann A1 Maude Jacquot A1 Joshua B. Singer A1 Kris De Clercq A1 Anette Bøtner A1 Corinne Sailleau A1 Cyrille Viarouge A1 Carrie Batten A1 Giantonella Puggioni A1 Ciriaco Ligios A1 Giovanni Savini A1 Piet A. van Rijn A1 Peter PC Mertens A1 Roman Biek A1 Massimo Palmarini YR 2019 UL http://biorxiv.org/content/early/2019/12/13/2019.12.11.872705.abstract AB The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the outbreak was successfully controlled through vaccination by early 2010, puzzlingly a closely-related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this period without replication, we conclude that the second outbreak was most likely initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.