Molecular epidemiology of dengue type 2 virus in Venezuela: evidence for in situ virus evolution and recombination

Epidemic outbreaks of dengue fever (DF) were first recorded in Venezuela in 1978 and were followed by the emergence of dengue haemorrhagic fever (DHF) outbreaks in 1989. To gain a better understanding of the nature of these e pidemics, the complete envelope (E) gene sequence of 34 Venezuelan dengue t ype 2 (DEN-2) viruses, isolated between 1997 and 2000 was determined. Of th ese isolates, 16 were from patients with DF and 17 were from patients diagn osed with DHF. There were no diagnostic sequence differences between them, suggesting that the E gene alone does not determine disease severity. These sequence data were also used in phylogenetic comparisons with a global sam ple of DEN-2 viruses, including strains collected previously from Venezuela . This analysis revealed that the ancestors of the Venezuelan viruses were Asian in origin, implying that a DEN-2 virus strain from this region was in troduced into Venezuela and the wider Caribbean region during the late 1970 s or the early 1980s. The phylogenetic trees further indicate that evolutio n of DEN-2 virus in Venezuela has occurred in situ, with differentiation in to a number of distinct but co-circulating lineages, rather than the repeat ed introduction of new strains from other localities. By incorporating addi tional sequence data from the virus capsid, premembrane and membrane genes, evidence is provided that a single Venezuelan strain sequenced previously, designated Mara4, is a recombinant virus, incorporating genome sequence fr om Venezuelan and Asian parental viruses.