Bayesian coalescent inference reveals high evolutionary rates and diversification of Zika virus populations

Abstract

Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered an epidemic in Brazil and spread across Latin America. By May of 2016, the World Health Organization warns over spread of ZIKV beyond this region. Detailed studies on the mode of evolution of ZIKV strains are extremely important for our understanding of the emergence and spread of ZIKV populations. In order to gain insight into these matters, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of recently isolated ZIKV strains was performed. The results of these studies revealed a mean rate of evolution of 1.20 × 10(-3) nucleotide substitutions per site per year (s/s/y) for ZIKV strains enrolled in this study. Several variants isolated in China are grouped together with all strains isolated in Latin America. Another genetic group composed exclusively by Chinese strains were also observed, suggesting the co-circulation of different genetic lineages in China. These findings indicate a high level of diversification of ZIKV populations. Strains isolated from microcephaly cases do not share amino acid substitutions, suggesting that other factors besides viral genetic differences may play a role for the proposed pathogenesis caused by ZIKV infection. J. Med. Virol. 88:1672-1676, 2016. © 2016 Wiley Periodicals, Inc.

Evidence of increasing diversification of Zika virus strains isolated in the American continent

“…As can be seen in Table , our results suggest that the ZIKV strains isolated in the American region evolved from ancestors that existed around February 20, 2014. This is in agreement with recent studies that estimate the tMRCA of Brazilian isolates between August 2013 and April 2014 or October 2013 and March 2014 …”

“…As can be seen in Table 1, our results suggest that the ZIKV strains isolated in the American region evolved from ancestors that existed around February 20, 2014. This is in agreement with recent studies that estimate the tMRCA of Brazilian isolates between August 2013 and April 2014 22,23 or October 2013 and March 2014. 24 When the GTR + Γ model is used, a mean rate of 1.55 × 10 −3 nucleotide substitutions per site per year (s/s/y) was obtained for the ZIKV strains included in these studies (Table 1).…”

“…When the GTR + Γ model is used, a mean rate of 1.55 × 10 −3 nucleotide substitutions per site per year (s/s/y) was obtained for the ZIKV strains included in these studies (Table ). This rate is comparable to the ones previously reported on the early stages of the ZIKV outbreak in the Americas (0.98‐1.06 × 10 −3 s/s/y and 1.20 × 10 −3 s/s/y) …”

“…In these studies, when the GTR + Γ model is used, a mean rate of 1.55 × 10 −3 s/s/y was obtained. This is comparable to the ones previously reported on the early stages of the ZIKV outbreak in the Americas and very recent studies revealing a substitution rate of 1.15 × 10 −3 s/s/y . As suggested for other RNA viruses, the differences observed among the different estimations may be related to the fact that the rapid initial epidemic spread and short timescale included in the initial analysis had resulted in a proportion of mildly deleterious mutations being maintained in the population.…”

Assessing the global threat from Zika virus

“…Recent evidence suggests distinct codon preferences between African and Asian ZIKV lineages, although adaptive genetic changes that may have an impact on viral replication and titers (141), while the genetic diversity of viruses isolated in ZIKV associated microcephaly cases suggest recent mutations may not be involved (142). Epidemiologic and laboratory studies are needed to determine if these changes have had a substantive effect on viral pathogenesis.…”