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

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
PloS one | 2018

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.

Pubmed ID: 30550577

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


FLASH (tool)

RRID:SCR_005531

Open source software tool to merge paired-end reads from next-generation sequencing experiments. Designed to merge pairs of reads when original DNA fragments are shorter than twice length of reads. Can improve genome assemblies and transcriptome assembly by merging RNA-seq data.

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CD-HIT (tool)

RRID:SCR_007105

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software program for clustering biological sequences with many applications in various fields such as making non-redundant databases, finding duplicates, identifying protein families, filtering sequence errors and improving sequence assembly etc. It is very fast and can handle extremely large databases. CD-HIT helps to significantly reduce the computational and manual efforts in many sequence analysis tasks and aids in understanding the data structure and correct the bias within a dataset. The CD-HIT package has CD-HIT, CD-HIT-2D, CD-HIT-EST, CD-HIT-EST-2D, CD-HIT-454, CD-HIT-PARA, PSI-CD-HIT, CD-HIT-OTU and over a dozen scripts. * CD-HIT (CD-HIT-EST) clusters similar proteins (DNAs) into clusters that meet a user-defined similarity threshold. * CD-HIT-2D (CD-HIT-EST-2D) compares 2 datasets and identifies the sequences in db2 that are similar to db1 above a threshold. * CD-HIT-454 identifies natural and artificial duplicates from pyrosequencing reads. * CD-HIT-OTU cluster rRNA tags into OTUs The usage of other programs and scripts can be found in CD-HIT user''s guide. CD-HIT was originally developed by Dr. Weizhong Li at Dr. Adam Godzik''s Lab at the Burnham Institute (now Sanford-Burnham Medical Research Institute).

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RRID:SCR_008493

Software analysis package for molecular biology community. Automatically copes with data in variety of formats and allows transparent retrieval of sequence data from web. Libraries are provided with package. Provides toolkit for creating bioinformatics applications or workflows. Provides set of sequence analysis programs. Provided programs cover areas such as sequence alignment, rapid database searching with sequence patterns, protein motif identification, nucleotide sequence pattern analysis, codon usage analysis for small genomes, rapid identification of sequence patterns in large scale sequence sets, and presentation tools for publication.

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FigTree (tool)

RRID:SCR_008515

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RRID:SCR_008539

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BEAST (tool)

RRID:SCR_010228

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Cluster (tool)

RRID:SCR_013505

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RRID:SCR_014629

Web phylogeny server based on the maximum-likelihood principle.

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Tracer (tool)

RRID:SCR_019121

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Illumina MiSeq System (tool)

RRID:SCR_016379

MiSeq System offers wide range of sequencing applications. Capable of automated paired end reads and up to 15 Gb per run, delivering over 600 bases of sequence data per read. The library prep kits are optimized for variety of applications, including targeted gene, small genome, and amplicon sequencing, 16S metagenomics.

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