title: Chikungunya virus adaptation to a mosquito vector correlates with only few point mutations in the viral envelope glycoprotein.
abstract: Like most arthropod-borne viruses (arboviruses), chikungunya virus (CHIKV) is a RNA virus maintained in nature in an alternating cycle of replication between invertebrate and vertebrate hosts. It has been assumed that host alternation restricts arbovirus genome evolution and imposes fitness trade-offs. Despite their slower rates of evolution, arboviruses still have the capacity to produce variants capable to exploit new environments. To test whether the evolution of the newly emerged epidemic variant of CHIKV (E1-226V) is constrained by host alternation, the virus was alternately-passaged in hamster-derived BHK-21 cells and Aedes aegypti-derived Aag-2 cells. It was also serially-passaged in BHK-21 or Aag-2 cells to promote adaptation to one cell type and presumably, fitness cost in the bypassed cell type. After 30 passages, obtained CHIKV strains were genetically and phenotypically characterized using in vitro and in vivo systems. Serially- and alternately-passaged strains can be distinguished by amino-acid substitutions in the E2 glycoprotein, responsible for receptor binding. Two substitutions at positions E2-64 and E2-208 only lower the dissemination of the variant E1-226V in Ae. aegypti. These amino-acid changes in the E2 glycoprotein might affect viral infectivity by altering the interaction between CHIKV E1-226V and the cellular receptor on the midgut epithelial cells in Ae. aegypti but not in Aedesalbopictus.
authors.affiliation: Department of Virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France; Cellule Pasteur UPMC, Université Pierre et Marie Curie, Paris, France. Electronic address: camilo.arias-goeta@pasteur.fr.
authors.forename: Camilo
authors.initials: C
authors.lastname: Arias-Goeta
authors.affiliation: Department of Virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Moutailler
authors.affiliation: Department of Virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Mousson
authors.affiliation: Department of Virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Zouache
authors.affiliation: Department of Infection and Epidemiology, Genotyping of Pathogens and Public Health, Institut Pasteur, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Thiberge
authors.affiliation: Department of Infection and Epidemiology, Genotyping of Pathogens and Public Health, Institut Pasteur, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Caro
authors.affiliation: URA 2581, Genetic and Molecular Interactions Cell-eucaryote, Institut Pasteur, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Rougeon
authors.affiliation: Department of Virology, Arboviruses and Insect Vectors, Institut Pasteur, Paris, France.
authors.forename: Anna-Bella
authors.initials: AB
authors.lastname: Failloux
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D006224:Cricetinae; D009033:Culicidae / Q000821:virology*; D019143:Evolution, Molecular; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics; D007303:Insect Vectors / Q000821:virology; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014759:Viral Envelope Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D016898:Interferon-alpha; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D016899:Interferon-beta
keywords: Arbovirus evolution; Genome stability; Host alternation; Vector adaptation