Global transmission and evolutionary dynamics of the Chikungunya virus

Abstract

Chikungunya virus (CHIKV) is a re-emerging pathogen of global importance. We attempted to gain an insight into the organisation, distribution and mutational load of the virus strains reported from different parts of the world. We describe transmission dynamics and genetic characterisation of CHIKV across the globe during the last 65 years from 1952 to 2017. The evolutionary pattern of CHIKV was analysed using the E1 protein gene through phylogenetic, Bayesian and Network methods with a dataset of 265 sequences from various countries. The time to most recent common ancestor of the virus was estimated to be 491 years ago with an evolutionary rate of 2.78 × 10-4 substitutions/site/year. Genetic characterisation of CHIKV strains was carried out in terms of variable sites, selection pressure and epitope mapping. The neutral selection pressure on the E1 gene of the virus suggested a stochastic process of evolution. We identified six potential epitope peptides in the E1 protein showing substantial interaction with human MHC-I and MHC-II alleles. The present study augments global epidemiological and population dynamics of CHIKV warranting undertaking of appropriate control measures. The identification of epitopic peptides can be useful in the development of epitope-based vaccine strategies against this re-emerging viral pathogen.

Keywords: Bayesian analysis; Chikungunya virus; docking; entropy; networking; phylogenetics; selection pressure.

Fig. 1.

The world map showing the distribution of different lineages of the Chikungunya virus. Regions with the evidence of well-established CHIKV circulation are circled whereas imported cases of CHIKV are denoted by stars in the map. (The map was downloaded from the site: https://commons.wikimedia.org/wiki/Atlas_of_the_world#/media/File:Whole_world_-_land_and_oceans_12000.jpg.)

Fig. 2.

The ML phylogenetic tree of the Chikungunya virus. The tree was generated by 1000 bootstrap values using partial E1 gene sequences. Bootstrap values more than 80% are shown at nodes.

Fig. 3.

The phylogenetic Network showing clusters of the Chikungunya virus sequences from different geographical regions. The network shows the pattern of emergence of CHIKV related to the first isolated strains. The size of the circles is representative of the number of clustering haplotypes from different parts of the world. The sequences in panels a, b and c show probable origin of the virus in ECSA strains, the distinct epidemic strains and the initial Asian strains. The cluster highlighted with a black circle contains recently circulating strains of Brazil, Mexico, the Caribbean and Micronesia. The arrows show the divergence of new and recently reported strains from their origin. The length of lines and distances between strains are not proportional to the mutational distances amongst these strains.

Fig. 4.

The MCMC Bayesian tree generated using different Chikungunya virus strains from various parts of the world. The age is mentioned on major branches with HPD 95% height.

Fig. 5.

The Bayesian skyline plot. The plot shows viral population vs. time of circulation of the Chikungunya virus strains from India.

Fig. 6.

Docking of the potential epitopes of the E1 protein of the Chikungunya virus with MHCI/II alleles. The images a, b and c show the interaction of HLA-A*35:01 with the three selected epitopes for MHCI molecules (details in the Supplementary Table S4). The images d, e and f show the interaction of HLA-DRB0101 with the first, second and fourth epitopes selected for MHCII molecules (details in the Supplementary Table S5).