Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak
Autor(es): Schuffenecker Isabelle, Iteman Isabelle, Michault Alain, Murri Séverine, Frangeul Lionel, Vaney Marie-Christine, Lavenir Rachel, Pardigon Nathalie, Reynes Jean-Marc, Pettinelli François, Biscornet Leon, Diancourt Laure, Michel Stéphanie, Duquerroy Stéphane, Guigon Ghislaine, Frenkiel Marie-Pascale, Bréhin Anne-Claire, Cubito Nadège, Desprès Philippe, Kunst Frank, Rey Félix A, Zeller Hervé, Brisse Sylvain
Resumo: A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Isl-, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful - 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. We report the nearly complete genome sequence of six selected viral isolates (isolated from five sera - one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, - Mayotte isl-s. 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, - RNA triphosphatase activities) - of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), - nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V - 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 - 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. The unique molecular features of the analyzed Indian Ocean isolates of chikungunya virus demonstrate their high evolutionary potential - suggest possible clues for underst-ing the atypical magnitude - virulence of this outbreak.
Imprenta: PLoS Medicine, v. 3, n. 7, p. e263, 2006
Identificador do objeto digital: 10.1371/journal.pmed.0030263
Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Biosynthesis ; Chikungunya virus - DNA ; Chikungunya virus - Genome ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya virus - Molecular methods ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemiology ; Chikungunya virus - Public health
Data de publicação: 2006
