Evidence for recombination in natural populations of dengue virus type 1 based on the analysis of complete genome sequences

Recombination events are known to occur in non-segmented RNA viruses like p olioviruses or alphaviruses. Analysis of the subgenomic sequences of dengue virus type 1 (DENV-1) structural genes has recently allowed the identifica tion of possible recombination breakpoints. Because DENV is a major human p athogen, this discovery might have important implications for virus pathoge nicity, vaccine safety and efficiency, or diagnosis and, therefore, require s clear confirmation. We report the complete sequence determination of one Asian and two African strains of DENV-1 isolated from human patients. Rigor ous sequence analysis provided strong evidence for the occurrence of intrag enomic recombination events between DENV-1 strains belonging to different l ineages. Singapore S275/90 strain appears to be the evolutionary product of a recombination event between viruses belonging to two distinct lineages: one lineage includes an African strain isolated in Abidjan (Ivory Coast) an d the other includes isolates from Djibouti and Cambodia. The 'Recombinatio n Detection Program', bootscanning and analysis of diversity plots provided congruent results concerning the existence of a two-switch recombination e vent and the localization of recombination breakpoints. Thus, the 5 ' and 3 ' genomic ends of the Singapore S275/90 strain were inherited from a Djibo uti/Cambodia lineage ancestor and an internal fragment located in the envel ope/NS1 region originated from an Abidjan lineage ancestor.