Chikungunya virus: evolution and genetic determinants of emergence

Abstract

Chikungunya virus (CHIKV) causes a severe and often persistent arthralgic disease that is occasionally fatal. A mosquito-borne virus, CHIKV exists in enzootic, non-human primate cycles in Africa, but occasionally emerges into urban, human cycles to cause major epidemics. Between 1920 and 1950, and again in 2005, CHIKV emerged into India and Southeast Asia, where major urban epidemics ensued. Unlike the early introduction, the 2005 emergence was accompanied by an adaptive mutation that allowed CHIKV to exploit a new epidemic vector, Aedes albopictus, via an A226V substitution in the E1 envelope glycoprotein. However, recent reverse genetic studies indicate that lineage-specific epistatic restrictions can prevent this from exerting its phenotype on mosquito infectivity. Thus, the A. albopictus-adaptive A226V substitution that is facilitating the dramatic geographic spread CHIKV epidemics, was prevented for decades or longer from being selected in most African enzootic strains as well as in the older endemic Asian lineage.

Fig. 1

Cartoon depicting the transmission cycles of chikungunya virus.

Fig. 2

Map showing the geographic distribution of CHIKV genotypes and the movement of CHIK outbreaks during 2004–2011. Triangles show countries with CHIKV importation via infected travelers. Based on references [13,15,30,33,53], data from Pubmed, PromedMail.org the Centers for Disease Control and Prevention (www.cdc.gov).

Fig. 3

Phylogenetic tree derived from all complete genomic CHIKV sequences available in the GenBank library, excluding some early, high passage isolates and a 2000 Indian isolate of suspected origin [28].

Fig. 4

Chikungunya E1–E2 heterodimer (pdb ID 3N44, chains B and F, [4]) fitted into cryo-electron microscopy map of the alphavirus, western equine encephilitis virus (WEEV; a chikungunya map is not available) [54]. A. 3D WEEV cryoEM map showing E1–E2 spikes on the surface of the virus. B. Top view of a spike from the map with an E1–E2 heterodimer fitted into the density. Part of E1 is projecting out from the density owing to the restricted size of the spike density cut out from the WEEV map. C. Side view of the spike with an E1–E2 heterodimer within the density. D. The spike rotated to show the amino acid residues in the E1–E2 structure involved in the mosquito host range. E. E1–E2 structure [4] in the same orientation as in D. with amino acid residues involved in the mosquito host range labeled (shown as orange red spheres). The Figure was prepared using Chimera.