A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential
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Open Access
- 7 December 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Pathogens
- Vol. 3 (12), e201
- https://doi.org/10.1371/journal.ppat.0030201
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. Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics of arthritic disease, including one on Reunion island, where there were approximately 266,000 cases (34% of the total island population). CHIKV is transmitted by Aedes species mosquitoes, primarily Ae. aegypti. However, the 2005–2006 CHIKV epidemic on Reunion island was unusual because the vector responsible for transmission between humans was apparently the Asian tiger mosquito, Ae. albopictus. Interestingly, the same epidemic was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V). In this work we investigated the role of the E1-A226V mutation on the fitness of CHIKV in Ae. aegypti and Ae. albopictus mosquitoes. We found that E1-A226V is directly responsible for CHIKV adaptation to Ae. albopictus mosquitoes, which provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This research gives a new insight into how a simple genetic change in a human pathogen can increase its host range and therefore its geographic distribution. Ae. albopictus is abundant and widely distributed in urban areas of Europe and the United States of America, and this work suggests that these areas are now vulnerable to CHIKV establishment.This publication has 57 references indexed in Scilit:
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