title: Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak.
abstract: BACKGROUND
  A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.
  
  
  RESULTS
  We report the nearly complete genome sequence of six selected viral isolates (isolated from five sera and one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, and Mayotte islands. Our results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, four of which were located in alphavirus-conserved positions of nsP2 (which contains helicase, protease, and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for membrane fusion and virion assembly. Change E1-A226V was absent in the initial strains but was observed in >90% of subsequent viral sequences from Réunion, denoting evolutionary success possibly due to adaptation to the mosquito vector.
  
  
  CONCLUSIONS
  The unique molecular features of the analyzed Indian Ocean isolates of chikungunya virus demonstrate their high evolutionary potential and suggest possible clues for understanding the atypical magnitude and virulence of this outbreak.
authors.affiliation: Centre National de Référence des Arbovirus, Institut Pasteur, Lyon, France. schuffenecker@cervi-lyon.inserm.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schuffenecker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Iteman
authors.forename: Alain
authors.initials: A
authors.lastname: Michault
authors.forename: Séverine
authors.initials: S
authors.lastname: Murri
authors.forename: Lionel
authors.initials: L
authors.lastname: Frangeul
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vaney
authors.forename: Rachel
authors.initials: R
authors.lastname: Lavenir
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pardigon
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reynes
authors.forename: François
authors.initials: F
authors.lastname: Pettinelli
authors.forename: Leon
authors.initials: L
authors.lastname: Biscornet
authors.forename: Laure
authors.initials: L
authors.lastname: Diancourt
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Michel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Duquerroy
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Guigon
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Frenkiel
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Bréhin
authors.forename: Nadège
authors.initials: N
authors.lastname: Cubito
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Frank
authors.initials: F
authors.lastname: Kunst
authors.forename: Félix A
authors.initials: FA
authors.lastname: Rey
authors.forename: Hervé
authors.initials: H
authors.lastname: Zeller
authors.forename: Sylvain
authors.initials: S
authors.lastname: Brisse
mesh_terms: D018354:Alphavirus Infections / Q000453:epidemiology* / Q000235:genetics*; D001483:Base Sequence; D002555:Cerebrospinal Fluid / Q000821:virology; D002646:Chikungunya virus / Q000235:genetics* / Q000302:isolation & purification; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007118:Immunoassay; D007195:Indian Ocean Islands / Q000453:epidemiology; D010641:Phenotype; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA