A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential

Abstract

Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics. The 2005–2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V). To test the hypothesis that this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness for different vector species, viral infectivity, dissemination, and transmission of CHIKV were compared in Aedes albopictus, the species implicated in the epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of the Reunion strain and a West African strain of CHIKV, into which either the E1–226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus, and led to more efficient viral dissemination into mosquito secondary organs and transmission to suckling mice. This mutation caused a marginal decrease in CHIKV Ae. aegypti midgut infectivity, had no effect on viral dissemination, and was associated with a slight increase in transmission by Ae. aegypti to suckling mice in competition experiments. The effect of the E1-A226V mutation on cholesterol dependence of CHIKV was also analyzed, revealing an association between cholesterol dependence and increased fitness of CHIKV in Ae. albopictus. Our observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area. Due to the widespread distribution of Ae. albopictus, this mutation increases the potential for CHIKV to permanently extend its range into Europe and the Americas.

Accidental discovery and isolation of Zika virus in Uganda and the relentless epidemiologist behind the investigations

“…Prior to this, CHIKV was not known to cause death in humans, then was transformed from nearly harmless to deadly. In comparison to the east African strain, the virus from Reunion Island had a single mutation of A226V in the envelope E1 protein (Tsetsarkin et al, 2007). Detailed analyses showed that this single mutation influenced vector fitness and viral infectivity.…”

Global epidemiology of Zika and Chikungunya virus human infections

“…albopictus, thus originating the ECSA Indian Ocean lineage (IOL) genotype (124). The E1-226V variant was more efficiently transmitted by A. albopictus (137), with a roughly 40-fold more efficient initial infection of midgut epithelial cells. The selection of the E1-226V variant occurs at the initial infection of the midgut of A. albopictus, leading to a higher viral dissemination and transmission of the IOL genotype by this mosquito.…”

“…albopictus, this mutation is limited to CHIKV ECSA strains, and other mutations in E1 and E2 have been found to block the A226V E1-mediated adaptation to Ae. albopictus (137).…”

Emerging alphaviruses in the Americas: Chikungunya and Mayaro

“…A vigorous immune response limits the disease produced by CHIKV and confers protection from re-infection. Thus, the migration of monocyte/macrophages into the synovial tissues likely contributes to the infl ammation of joints and may explain the persistence of arthritis despite the lack of viremia 16 . In addition, the persistence of CHIKV in the joints of monkeys has been associated with chronic arthropathy.…”