Viral outbreaks involve destabilized evolutionary networks: evidence from Ebola, Influenza and Zika

Abstract

Recent history has provided us with one pandemic (Influenza A/H1N1) and two severe viral outbreaks (Ebola and Zika). In all three cases, post-hoc analyses have given us deep insights into what triggered these outbreaks, their timing, evolutionary dynamics, and phylogeography, but the genomic characteristics of outbreak viruses are still unclear. To address this outstanding question, we searched for a common denominator between these recent outbreaks, positing that the genome of outbreak viruses is in an unstable evolutionary state, while that of non-outbreak viruses is stabilized by a network of correlated substitutions. 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 substitutions targeting epitopes, but more likely by changes in the environment sensu lato. Our results prompt for a new interpretation of pandemics as being associated with evolutionary destabilized viruses.

Artificial Intelligence (AI) Provided Early Detection of the Coronavirus (COVID-19) in China and Will Influence Future Urban Health Policy Internationally

“…On this, though detection times may vary greatly in respect virus types (influenza, Henipavirus (Nipah virus), Filoviruses like Ebola, and Flavivirus like Zika et cetera) [16,17] and other characteristics, the constant is that technological advancement is clearly aiding in reducing their detection time. This was evidenced in the recent case of COVID-19, taking only seven days for detection.…”

Episodic diversifying selection and intragenomic interactions shape the evolution of DNA and RNA viruses

“…Note however that this latter analysis is more informative than the former, as the density also shows that most of the sites under selection are involved in weak interactions. This is intriguingly reminiscent of the involvement of weakly interacting pairs of sites in severe outbreaks or pandemics (Aris-Brosou et al ., 2017).…”

“…These reconstructed mutational paths were then recoded as a binary matrix, with rows corresponding to branches and columns to a site of the alignment. The BGM was then used to identify the pairs of sites that exhibit correlated patterns of nonsynonymous substitutions according to their posterior probability, estimated with a Markov chain Monte Carlo sampler that was run for 10 5 steps, with a burn-in period of 10,000 steps sampling every 1,000 steps for inference (Aris-Brosou et al ., 2017).…”

“…This last point suggests that a seldom explored evolutionary process, correlated evolution, might play a key role in the evolution of these single-stranded viruses. Indeed, recent work uncovered pervasive evidence for correlated evolution in influenza viruses (Nshogozabahizi et al ., 2017), and both the Zika (Aris-Brosou et al ., 2017) and the Ebola viruses (Ibeh et al ., 2016), with evidence in the latter that sites evolving in a correlated manner can also be under episodic diversifying selection. However, this recent body of evidence is so far limited to a small number of ssRNA viruses, so that the combined role of correlated evolution and selection is difficult to generalize.…”

Viral Long-Term Evolutionary Strategies Favor Stability over Proliferation

“…To date, however, correlated evolution has only sporadically been investigated in viral evolution, and these rare instances only focused on ssRNA viruses. Indeed, recent work uncovered pervasive evidence for correlated evolution in influenza viruses [14,15], and both the Zika [16] and the Ebola viruses [17]. Intriguingly, in this latter case (Ebola), evidence was found that sites evolving in a correlated manner could also be under positive selection—bearing the question as to how frequently these two processes, correlated evolution and positive selection, occur, possibly jointly, and if this co-occurrence is limited to ssRNA viruses, or can be generalized to all viruses.…”