“Frozen evolution” of an RNA virus suggests accidental release as a potential cause of arbovirus re-emergence

by David J. Pascall, Kyriaki Nomikou, Emmanuel Bréard, Stephan Zientara, Ana da Silva Filipe, Bernd Hoffmann, Maude Jacquot, Joshua B. Singer, Kris De Clercq, Anette Bøtner, Corinne Sailleau, Cyril Viarouge, Carrie Batten, Giantonella Puggioni, Ciriaco Ligios, Giovanni Savini, Piet A. van Rijn, Peter P. C. Mertens, Roman Biek, Massimo Palmarini

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-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.

Although 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 long period without replication, we hypothesise that the second outbreak could have been 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.