Abstract

Chikungunya virus (CHIKV) has been detected sporadically since the 1950s and includes three distinct co-circulating genotypes. In late 2013, the Asian genotype of CHIKV was responsible for the Caribbean outbreak (CO) that rapidly became an epidemic throughout the Americas. There is a limited understanding of the molecular evolution of CHIKV in the Americas during this epidemic. We sequenced 185 complete CHIKV genomes collected mainly from Nicaragua in Central America and Florida in the United States during the 2014–2015 Caribbean/Americas epidemic. Our comprehensive phylogenetic analyses estimated the epidemic history of the Asian genotype and the recent Caribbean outbreak (CO) clade, revealed considerable genetic diversity within the CO clade, and described different epidemiological dynamics of CHIKV in the Americas. Specifically, we identified multiple introductions in both Nicaragua and Florida, with rapid local spread of viruses in Nicaragua but limited autochthonous transmission in Florida in the US. Our phylogenetic analysis also showed phylogeographic clustering of the CO clade. In addition, we identified the significant amino acid substitutions that were observed across the entire Asian genotype during its evolution and examined amino acid changes that were specific to the CO clade. Deep sequencing analysis identified specific minor variants present in clinical specimens below-consensus levels. Finally, we investigated the association between viral phylogeny and geographic/clinical metadata in Nicaragua. To date, this study represents the largest single collection of CHIKV complete genomes during the Caribbean/Americas epidemic and significantly expands our understanding of the emergence and evolution of CHIKV CO clade in the Americas.

Highlights

  • Chikungunya virus (CHIKV) belongs to the Alphavirus genus in the Togaviridae family and is an arthropod-borne virus spread by Aedes mosquitoes

  • CHIKV infections in the United States were primarily reported in Florida, with sporadic cases of traveler-associated infection reported in other states

  • Despite multiple introductions, limited local transmission was documented in Florida; in contrast, in Nicaragua, rapid local dissemination was observed

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Summary

Introduction

Chikungunya virus (CHIKV) belongs to the Alphavirus genus in the Togaviridae family and is an arthropod-borne virus spread by Aedes mosquitoes. CHIKV was detected sporadically in limited regions in Africa and Asia until the early 2000s [5,6,7,8]. Three distinct genotypes of CHIKV have been identified: West African, Asian, and East/Central/South African (ECSA) [9]. In 2005, the CHIKV ECSA genotype reemerged and caused multiple explosive epidemics across Africa, Asia, and the Indian Ocean, which subsided [10,11,12,13]. In late 2013, the CHIKV Asian genotype was introduced into the Americas and rapidly spread through numerous Caribbean, South American, and Central American countries via Aedes aegypti mosquitoes [14,15,16]

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