title: 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.
authors.affiliation: Division of Virology, Defence R and D Establishment, Jhansi Road, Gwalior 474002, M.P., India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Vector Management Division, Defence R and D Establishment, Jhansi Road, Gwalior 474002, M.P., India.
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Sharma
authors.affiliation: Vector Management Division, Defence R and D Establishment, Jhansi Road, Gwalior 474002, M.P., India.
authors.forename: D
authors.initials: D
authors.lastname: Sukumaran
authors.affiliation: Division of Virology, Defence R and D Establishment, Jhansi Road, Gwalior 474002, M.P., India.
authors.forename: Manmohan
authors.initials: M
authors.lastname: Parida
authors.affiliation: Division of Virology, Defence R and D Establishment, Jhansi Road, Gwalior 474002, M.P., India. Electronic address: pabandash@drde.drdo.in.
authors.forename: Paban Kumar
authors.initials: PK
authors.lastname: Dash
mesh_terms: D000220:Adaptation, Biological; D000330:Aedes / Q000821:virology*; D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D065632:Chikungunya Fever / Q000635:transmission / Q000821:virology; D002646:Chikungunya virus / Q000145:classification / Q000235:genetics*; D056084:Genetic Fitness; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D008958:Models, Molecular; D009154:Mutation; D010802:Phylogeny; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012367:RNA, Viral; D012641:Selection, Genetic; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins
keywords: Aedes; Chikungunya; Dissemination; Infection; Mutations; Transmission