title: Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.
abstract: BACKGROUND
  Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak.
  
  
  RESULTS
  We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells.
  
  
  CONCLUSIONS
  Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV.
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Stapleford
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Moratorio
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.|Institut Pasteur, International Group for Data Analysis, Paris, France.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Henningsson
authors.affiliation: Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Rubing
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institut Pasteur de la Guyane, Laboratoire de Virologie, Centre National de Référence des Arbovirus, Cayenne, French Guiana.
authors.forename: Séverine
authors.initials: S
authors.lastname: Matheus
authors.affiliation: Institut Pasteur de la Guyane, Laboratoire de Virologie, Centre National de Référence des Arbovirus, Cayenne, French Guiana.
authors.forename: Antoine
authors.initials: A
authors.lastname: Enfissi
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Blanc
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Mounce
authors.affiliation: Institut Pasteur de Nouvelle-Calédonie, Research and Expertise Unit on Dengue and other Arboviruses, Noumea, New Caledonia.
authors.forename: Myrielle
authors.initials: M
authors.lastname: Dupont-Rouzeyrol
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.affiliation: Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Weaver
authors.affiliation: Institut Pasteur, International Group for Data Analysis, Paris, France.
authors.forename: Magnus
authors.initials: M
authors.lastname: Fontes
authors.affiliation: Institut Pasteur de la Guyane, Laboratoire de Virologie, Centre National de Référence des Arbovirus, Cayenne, French Guiana.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rousset
authors.affiliation: Institut Pasteur, Centre National de la Recherche Scientifique UMR 3569, Viral Populations and Pathogenesis Unit, Paris, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Vignuzzi
mesh_terms: D017691:Caribbean Region / Q000453:epidemiology; D065632:Chikungunya Fever / Q000453:epidemiology / Q000821:virology*; D002646:Chikungunya virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA