Origin, evolution, and phylogeography of recent epidemic CHIKV strains.

Chikungunya virus (CHIKV) is an arthropod-borne virus of the Alphavirus genus, which is transmitted to humans by Aedes spp. mosquitoes and was firstly identified in Tanzania in the mid 1950s. In this article, the findings of a phylogenetic and phylogeographic analysis of the recent CHIKV pandemic are reported. We estimated time of origin of the ancestral virus, time and place of occurrence of A226V mutation, and the flow of viral strains from an area to the other. The Bayesian phylogenetic and phylogeographic analysis was performed on the whole dataset, which consisted of 195 E1 (envelope 1) CHIKV sequences, and on a subset (D2), including 146 of the 195 previous sequences. Using the relaxed clock model, we estimated a CHIKV E1 mean evolutionary rate (in the whole dataset) of 1.4 × 10(-3)substitution/site/year (95% highest posterior density interval HPD 6.4 × 10(-4)-2.5 × 10(-3)), and of 2.2 × 10(-3) (95% HPD 9.6 × 10(-4)-3.8 × 10(-3)) in the D2 subset, including only the strains involved in the recent Indian Ocean epidemic. The phylogeographical analysis suggested an African origin of CHIKV with a tMRCA of 146 years corresponding to 1863 (95% HPD 1741-1941). Moreover D2 subset most probably originated in Kenya, with a tMRCA corresponding to the year 2002 (95% HPD 2000-2004), then spread following two distinct routes: one throughout the Indian Ocean (Reunion, Comoros) and the other moving from India then scattered in the South East Asia and reached Italy. In conclusion, we reconstructed the geographic spread of CHIKV during the last epidemic wave, which showed an eastward path from Africa to Indian Ocean island to India, and from there to other South East Asian countries. Whether A226V variants followed the same migration path remains undefined, since local independent mutations, followed by fixation due to selective advantage conferred by better adaptation to local vectors of infection, cannot be excluded.