Interspecies transmission and chikungunya virus emergence

Abstract

Chikungunya virus (CHIKV) causes severe, debilitating, often chronic arthralgia with high attack rates, resulting in severe morbidity and economic costs to affected communities. Since its first well-documented emergence in Asia in the 1950s, CHIKV has infected millions and, since 2007, has spread widely, probably via viremic travelers, to initiate urban transmission in Europe, the South Pacific, and the Americas. Some spread has been facilitated by adaptive envelope glycoprotein substitutions that enhance transmission by the new vector, Aedes albopictus. Although epistatic constraints may prevent the impact of these mutations in Asian strains now circulating in the Americas, as well as in African CHIKV strains imported into Brazil last year, these constraints could eventually be overcome over time to increase the transmission by A. albopictus in rural and temperate regions. Another major determinant of CHIKV endemic stability in the Americas will be its ability to spill back into an enzootic cycle involving sylvatic vectors and nonhuman primates, an opportunity exploited by yellow fever virus but apparently not by dengue viruses.

Figure 1

Phylogenetic tree showing the relationships among enzootic and endemic/epidemic CHIKV lineages and a time estimate for introduction of the Asian lineage from Africa into Asia; sl indicates IOL sublineage with second-step A. albopictus-adaptive mutations [56]. The tree was generated using concatenated open reading frames from all complete genomic sequences found in the Genbank library using maximum likelihood implemented in PAUP 4.0 [64]. The branch colors represent countries or regions of origin for each CHIKV sample. The scale indicates nucleotide sequence divergence.

Figure 2

Map showing the historic spread of CHIKV from enzootic cycles in Africa to Asia, Europe and the Americas.

Figure 3

Cartoon showing enzootic and urban CHIKV transmission cycles and their connection in sub-Saharan Africa.