TY - JOUR T1 - Viral outbreaks involve destabilized viruses: evidence from Ebola, Influenza and Zika JF - bioRxiv DO - 10.1101/070102 SP - 070102 AU - Stéphane Aris-Brosou AU - Neke Ibeh AU - Jessica Noël Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/26/070102.abstract N2 - Recent history has provided us with two severe viral outbreaks (Ebola and Zika) and one pandemic (Influenza A/H1N1). In all three cases, post-hoc analyses have given us deep insights into what triggered these outbreaks, their timing, evolutionary dynamics, and their phylogeography, but the genomic characteristics of outbreak viruses are still unclear. To address this outstanding question, we searched for a common denominator of these recent outbreaks, positing that genomes of outbreak viruses are in an unstable evolutionary state, while those of non-outbreak viruses are stabilized by a network of correlated substitutions that have been found to be prevalent. Here, we show that during regular epidemics, viral genomes are indeed stabilized by a dense network of weakly correlated sites, and that these networks disappear during pandemics and outbreaks when rates of evolution increase transiently. Post-pandemic, these evolutionary networks are progressively re-established. We finally show that destabilization is not caused by mutations targeting epitopes, but more likely by changes in the environment sensu lato. Our results prompt for a new interpretation of pandemics as being caused by, from an evolutionary standpoint, destabilized, unhealthy viruses. ER -