title: Emergence and transmission of arbovirus evolutionary intermediates with epidemic potential.
abstract: The high replication and mutation rates of RNA viruses can result in the emergence of new epidemic variants. Thus, the ability to follow host-specific evolutionary trajectories of viruses is essential to predict and prevent epidemics. By studying the spatial and temporal evolution of chikungunya virus during natural transmission between mosquitoes and mammals, we have identified viral evolutionary intermediates prior to emergence. Analysis of virus populations at anatomical barriers revealed that the mosquito midgut and salivary gland pose population bottlenecks. By focusing on virus subpopulations in the saliva of multiple mosquito strains, we recapitulated the emergence of a recent epidemic strain of chikungunya and identified E1 glycoprotein mutations with potential to emerge in the future. These mutations confer fitness advantages in mosquito and mammalian hosts by altering virion stability and fusogenic activity. Thus, virus evolutionary trajectories can be predicted and studied in the short term before new variants displace currently circulating strains.
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Stapleford
authors.affiliation: Center for Vectorborne Diseases, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, One Shields Avenue, 5327 VM3A, Davis, CA 95616, USA.
authors.forename: Lark L
authors.initials: LL
authors.lastname: Coffey
authors.affiliation: Virology Unit, Institut Pasteur in Cambodia 5, Monivong Boulevard, PO Box 983, Phnom Penh, Cambodia.
authors.forename: Sreyrath
authors.initials: S
authors.lastname: Lay
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Bordería
authors.affiliation: Virology Unit, Institut Pasteur in Cambodia 5, Monivong Boulevard, PO Box 983, Phnom Penh, Cambodia.
authors.forename: Veasna
authors.initials: V
authors.lastname: Duong
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rozen-Gagnon
authors.affiliation: Arboviruses and Insect Vectors Lab, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Camilo
authors.initials: C
authors.lastname: Arias-Goeta
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Blanc
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beaucourt
authors.affiliation: Department of Chemical Engineering and Polymer Research Center, Boğaziçi University, Bebek 34342, Istanbul, Turkey.
authors.forename: Türkan
authors.initials: T
authors.lastname: Haliloğlu
authors.affiliation: Ultrastructural Microscopy Platform, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Schmitt
authors.affiliation: Ultrastructural Microscopy Platform, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bonne
authors.affiliation: Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Ben-Tal
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.affiliation: Arboviruses and Insect Vectors Lab, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Anna-Bella
authors.initials: AB
authors.lastname: Failloux
authors.affiliation: Virology Unit, Institut Pasteur in Cambodia 5, Monivong Boulevard, PO Box 983, Phnom Penh, Cambodia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.affiliation: Viral Populations and Pathogenesis Unit, Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, 28 rue du Dr Roux, 75724 Paris Cedex 15, France. Electronic address: marco.vignuzzi@pasteur.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Vignuzzi
mesh_terms: D000330:Aedes / Q000821:virology; D000818:Animals; D001102:Arbovirus Infections / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D001103:Arboviruses / Q000472:pathogenicity* / Q000502:physiology*; D005075:Biological Evolution; D002160:Cambodia; D065632:Chikungunya Fever / Q000635:transmission / Q000821:virology; D002646:Chikungunya virus / Q000235:genetics / Q000472:pathogenicity; D009033:Culicidae / Q000821:virology*; D004195:Disease Models, Animal; D058872:Epidemics; D005260:Female; D014644:Genetic Variation; D054884:Host-Pathogen Interactions; D006801:Humans; D007303:Insect Vectors; D008322:Mammals / Q000821:virology; D008810:Mice, Inbred C57BL; D012463:Saliva / Q000821:virology; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics