Evolutionary analysis of the Chikungunya virus epidemic in Mexico reveals intra-host mutational hotspots in the E1 protein

PLoS One. 2018 Dec 14;13(12):e0209292. doi: 10.1371/journal.pone.0209292. eCollection 2018.

Abstract

The epidemic potential of Chikungunya virus (CHIKV) was recently made evident by its introduction and rapid expansion in the Caribbean and the Americas. We sought to gain a detailed understanding of the dynamics of the epidemic in Mexico, the country with the highest number of confirmed CHIKV cases in the Americas, and to characterise viral evolution at the population and intra-host level. Analysis of the spatiotemporal distribution of 2,739 diagnosed cases in Mexico from December 2014 to December 2015 showed a rapid nationwide expansion of the epidemic with focalisation in the South West of the country. We sequenced the envelope glycoprotein 1 gene (E1) from 25 patients using the Illumina MiSeq platform and report synonymous and non-synonymous consensus mutations. Bayesian phylogenetic analysis using 249 Asian lineage E1 sequences gave updated estimates of nucleotide substitution rates for E1 and time to most recent common ancestor of major lineages. The analysis indicates phylogenetically-related emergent Latin American clusters in South Western Mexico, Nicaragua and Honduras and transmission of American strains in the Pacific islands. Detailed analysis showed that intra-host changes in E1 mainly occurred in two variable regions (E1:189-220 and E1:349-358) in domains II and III, respectively, in residues involved in inter and intra-envelope spike interactions. At the population level, this study sheds light on the introduction and evolutionary dynamics of CHIKV in the Americas. At the intra-host level, this study identifies mutational hotspots of the E1 protein with implications for understanding the relationship between the CHIKV quasispecies, viral fitness and pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biodiversity
  • Chikungunya Fever / epidemiology*
  • Chikungunya Fever / transmission
  • Chikungunya virus / genetics*
  • Chikungunya virus / metabolism
  • Child
  • Consensus Sequence
  • Epidemics
  • Evolution, Molecular
  • Female
  • Genome, Viral
  • Geography, Medical
  • Humans
  • Male
  • Mexico
  • Middle Aged
  • Mutation*
  • Phylogeny
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / metabolism
  • Young Adult

Substances

  • E1 envelope protein, Chikungunya virus
  • Viral Envelope Proteins

Grants and funding

This study was supported by the Instituto Mexicano del Seguro Social (FIS/IMSS/PROT/G16/1575 to JEMM), the Secretaría de Educación Pública (103.5/16/10420 to MAGK), the Consejo Nacional de Ciencia y Tecnología (264598 to MAGK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.