Two novel epistatic mutations (E1:K211E and E2:V264A) in structural proteins of Chikungunya virus enhance fitness in Aedes aegypti

Abstract

Expansion of CHIKV outbreaks with appearance of novel mutations are reported from many parts of the world. Two novel mutations viz. E1:K211E and E2:V264A in background of E1:226A are recently identified from Aedes aegypti dominated areas of India. In this study, the role of these mutations in modulation of infectivity, dissemination and transmission by two different Aedes species was studied. Mutations were sequentially constructed in CHIKV genome and female Ae. aegypti and Aedes albopictus mosquitoes were orally infected with eight different CHIKV mutants. Double mutant virus containing E1:K211E and E2:V264A mutations in background of E1:226A revealed remarkably higher fitness for Ae. aegypti, as indicated by significant increase in virus infectivity (13 fold), dissemination (15 fold) and transmission (62 fold) compared to parental E1:226A virus. These results indicate that adaptive mutations in CHIKV are leading to efficient CHIKV circulation in Ae. aegypti endemic areas, contributing and sustaining the major CHIKV outbreaks.

First report of naturally infected Aedes aegypti with chikungunya virus genotype ECSA in the Americas

“…The mutations that enhance the fitness of the CHIKV genotype ECSA in Aedes mosquitoes were previously described [29,30] and they were not found in the genotype characterized in our study. However, new mutations that improve vector competence can be acquired since the ECSA genotype is being detected in other regions in Brazil [43], which suggests that different populations of Aedes mosquitoes are interacting with this recently introduced genotype, mainly Aedes aegypti in urban areas.…”

“…aegypti and Ae . albopictus [29,30] were not detected in envelope protein 1 (E1) from sequenced CHIKV.…”

The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies

“…Moreover, in a recent study by Hoornweg and colleagues, this mutation reinforced the cholesterol-dependent membrane fusion of the CHIKV with the host endosomal membranes [66]. In another recent paper, another two epistatic mutations (E1:K211E together with E2:V264A) were also found to notably enhance transmission (62 fold), infection (13 fold), and dissemination (15 fold) in Aedes aegypti mosquitos [141]. However, the exact mechanisms and possible interacting host factors that may facilitate the enhanced fitness of the virus are still unknown.…”

Impact of transmission cycles and vector competence on global expansion and emergence of arboviruses

“…A single genetic change in CHIKV E1:226A/V was associated with adaptation in Ae albopictus with high midgut infectivity and transmission potential . Novel adaptive mutations E1:K211E and E2:V264A led to higher fitness in Ae aegypti . Epizootic emergence by subtype IE VEEV was due a specific genetic determinant that contributed in increased infectivity and transmission .…”

“…89 Novel adaptive mutations E1:K211E and E2:V264A led to higher fitness in Ae aegypti. 90 Epizootic emergence by subtype IE VEEV was due a specific genetic determinant that contributed in increased infectivity and transmission. 91 Besides the genetic makeup of the vector and virus, some evolutionary forces also act on viral populations within the vector.…”