title: Molecular epidemiology of dengue type 2 virus in Venezuela: evidence for in situ virus evolution and recombination.
abstract: 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 epidemics, the complete envelope (E) gene sequence of 34 Venezuelan dengue type 2 (DEN-2) viruses, isolated between 1997 and 2000 was determined. Of these isolates, 16 were from patients with DF and 17 were from patients diagnosed 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 sample 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 introduced into Venezuela and the wider Caribbean region during the late 1970s or the early 1980s. The phylogenetic trees further indicate that evolution of DEN-2 virus in Venezuela has occurred in situ, with differentiation into a number of distinct but co-circulating lineages, rather than the repeated introduction of new strains from other localities. By incorporating additional 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 from Venezuelan and Asian parental viruses.
authors.affiliation: Centre for Ecology and Hydrology (CEH) Oxford, Formerly the Institute of Virology and Environmental Microbiology, Mansfield Road, Oxford OX1 3SR, UK1.
authors.forename: N Y
authors.initials: NY
authors.lastname: Uzcategui
authors.affiliation: Laboratorio Regional de Diagnóstico e Investigación del Dengue y otras enfermedades virales (Lardidev), Maracay, Estado Aragua, Venezuela3.
authors.forename: D
authors.initials: D
authors.lastname: Camacho
authors.affiliation: Laboratorio Regional de Diagnóstico e Investigación del Dengue y otras enfermedades virales (Lardidev), Maracay, Estado Aragua, Venezuela3.
authors.forename: G
authors.initials: G
authors.lastname: Comach
authors.affiliation: Instituto Venezolano de Investigaciones Científicas - IVIC, Centro de Microbiología y Biología Celular, Carretera Panamericana Km 11, Altos de Pipe, Apartado Postal 21827, Caracas 1020A, Venezuela4.
authors.forename: R
authors.initials: R
authors.lastname: Cuello de Uzcategui
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK2.
authors.forename: E C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Centre for Ecology and Hydrology (CEH) Oxford, Formerly the Institute of Virology and Environmental Microbiology, Mansfield Road, Oxford OX1 3SR, UK1.
authors.forename: E A
authors.initials: EA
authors.lastname: Gould
mesh_terms: D001208:Asia / Q000453:epidemiology; D003715:Dengue / Q000453:epidemiology*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D014687:Venezuela / Q000453:epidemiology; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins