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

Research output: Contribution to journalArticle

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 glyco-protein 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 intrahost 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.

Details

Authors
  • José Esteban Muñoz-Medina
  • Miguel Antonio Garcia-Knight
  • Alejandro Sanchez-Flores
  • Irma Eloísa Monroy-Muñoz
  • Ricardo Grande
  • Joakim Esbjörnsson
  • Clara Esperanza Santacruz-Tinoco
  • César Raúl González-Bonilla
Organisations
External organisations
  • Mexican Institute Of Social Security
  • Benemerita Autonomous University of Puebla
  • University of Oxford
  • University of California, San Francisco
  • National Autonomous University of Mexico
  • National Institute Of Perinatology (INPer)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Infectious Medicine
Original languageEnglish
Article numbere0209292
JournalPLoS ONE
Volume13
Issue number12
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes