title: Molecular evolution of dengue 2 virus in Puerto Rico: positive selection in the viral envelope accompanies clade reintroduction.
abstract: Dengue virus is a circumtropical, mosquito-borne flavivirus that infects 50-100 million people each year and is expanding in both range and prevalence. Of the four co-circulating viral serotypes (DENV-1 to DENV-4) that cause mild to severe febrile disease, DENV-2 has been implicated in the onset of dengue haemorrhagic fever (DHF) in the Americas in the early 1980s. To identify patterns of genetic change since DENV-2's reintroduction into the region, molecular evolution in DENV-2 from Puerto Rico (PR) and surrounding countries was examined over a 20 year period of fluctuating disease incidence. Structural genes (over 20 % of the viral genome), which affect viral packaging, host-cell entry and immune response, were sequenced for 91 DENV-2 isolates derived from both low- and high-prevalence years. Phylogenetic analyses indicated that DENV-2 outbreaks in PR have been caused by viruses assigned to subtype IIIb, originally from Asia. Variation amongst DENV-2 viruses in PR has since largely arisen in situ, except for a lineage-replacement event in 1994 that appears to have non-PR New World origins. Although most structural genes have remained relatively conserved since the 1980s, strong evidence was found for positive selection acting on a number of amino acid sites in the envelope gene, which have also been important in defining phylogenetic structure. Some of these changes are exhibited by the multiple lineages present in 1994, during the largest Puerto Rican outbreak of dengue, suggesting that they may have altered disease dynamics, although their functional significance will require further investigation.
authors.affiliation: Department of Biology, University of Puerto Rico - Rio Piedras, San Juan, PR, USA.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Bennett
authors.affiliation: Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA.
authors.forename: Maritza
authors.initials: M
authors.lastname: Chirivella
authors.affiliation: Department of Biology, University of Puerto Rico - Rio Piedras, San Juan, PR, USA.
authors.forename: Dania M
authors.initials: DM
authors.lastname: Rodriguez
authors.affiliation: Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA.
authors.forename: Manuela
authors.initials: M
authors.lastname: Beltran
authors.affiliation: Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA.
authors.forename: Vance
authors.initials: V
authors.lastname: Vorndam
authors.affiliation: Asia-Pacific Institute of Tropical Medicine and Infectious Diseases, Honolulu, HI, USA.
authors.forename: Duane J
authors.initials: DJ
authors.lastname: Gubler
authors.affiliation: Department of Biology, University of Puerto Rico - Rio Piedras, San Juan, PR, USA.
authors.forename: W Owen
authors.initials: WO
authors.lastname: McMillan
mesh_terms: D003715:Dengue / Q000453:epidemiology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011647:Puerto Rico / Q000453:epidemiology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D015678:Viral Structural Proteins / Q000235:genetics
chemical_list: D015678:Viral Structural Proteins