{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:46:01Z","timestamp":1791517561952,"version":"4.3.4"},"reference-count":50,"publisher":"Microbiology Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,4,1]]},"abstract":"<jats:p><jats:italic>Dengue virus<\/jats:italic>is a circumtropical, mosquito-borne flavivirus that infects 50\u2013100 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\u2005year period of fluctuating disease incidence. Structural genes (over 20\u200a% 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<jats:italic>in situ<\/jats:italic>, 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.<\/jats:p>","DOI":"10.1099\/vir.0.81309-0","type":"journal-article","created":{"date-parts":[[2006,3,9]],"date-time":"2006-03-09T23:22:50Z","timestamp":1141946570000},"page":"885-893","source":"Crossref","is-referenced-by-count":105,"title":["Molecular evolution of dengue 2 virus in Puerto Rico: positive selection in the viral envelope accompanies clade reintroduction"],"prefix":"10.1099","volume":"87","author":[{"given":"Shannon N.","family":"Bennett","sequence":"first","affiliation":[{"name":"Department of Biology, University of Puerto Rico \u2013 Rio Piedras, San Juan, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maritza","family":"Chirivella","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania M.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Puerto Rico \u2013 Rio Piedras, San Juan, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Beltran","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vance","family":"Vorndam","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention, Dengue Branch, San Juan, PR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane J.","family":"Gubler","sequence":"additional","affiliation":[{"name":"Asia-Pacific Institute of Tropical Medicine and Infectious Diseases, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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Virol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0042-6822(86)90200-X","article-title":"Nucleotide sequence and deduced amino acid sequence of the structural proteins of dengue type 2 virus, Jamaica genotype","volume":"155","author":"Deubel","year":"1986","journal-title":"Virology"},{"key":"R5","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/0042-6822(88)90677-0","article-title":"Nucleotide sequence and deduced amino acid sequence of the nonstructural proteins of dengue type 2 virus, Jamaica genotype: comparative analysis of the full-length genome","volume":"165","author":"Deubel","year":"1988","journal-title":"Virology"},{"key":"R6","first-page":"201","article-title":"The 1986 dengue and dengue hemorrhagic fever epidemic in Puerto Rico: epidemiologic and clinical observations","volume":"15","author":"Dietz","year":"1996","journal-title":"P R Health Sci J"},{"key":"R7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/S0042-6822(02)00033-8","article-title":"Molecular evolution and phylogeny of dengue type 4 virus in the Caribbean","volume":"306","author":"Foster","year":"2003","journal-title":"Virology"},{"key":"R8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.virol.2004.03.020","article-title":"Phylogeography and molecular evolution of dengue type 2 virus in the Caribbean basin, 1981\u20132000","volume":"324","author":"Foster","year":"2004","journal-title":"Virology"},{"key":"R9","first-page":"9","article-title":"Dengue and dengue hemorrhagic fever in the Americas","volume-title":"In Dengue Hemorrhagic Fever , WHO regional publication SEARO no. 22","author":"Gubler","year":"1993"},{"key":"R10","first-page":"1","article-title":"Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem","volume-title":"In Dengue and Dengue Hemorrhagic Fever","author":"Gubler","year":"1997"},{"key":"R11","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1128\/CMR.11.3.480","article-title":"Dengue and dengue hemorrhagic fever","volume":"11","author":"Gubler","year":"1998a","journal-title":"Clin Microbiol Rev"},{"key":"R12","first-page":"227","article-title":"The global pandemic of dengue\/dengue haemorrhagic fever: current status and prospects for the future","volume":"27","author":"Gubler","year":"1998b","journal-title":"Ann Acad Med Singapore"},{"key":"R13","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0966-842X(01)02288-0","article-title":"Epidemic dengue\/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century","volume":"10","author":"Gubler","year":"2002","journal-title":"Trends Microbiol"},{"key":"R14","doi-asserted-by":"crossref","first-page":"581","DOI":"10.4269\/ajtmh.1978.27.581","article-title":"Epidemiologic, clinical, and virologic observations on dengue in the Kingdom of Tonga","volume":"27","author":"Gubler","year":"1978","journal-title":"Am J Trop Med Hyg"},{"key":"R15","first-page":"213","article-title":"A study of fatal hemorrhagic dengue cases in Cuba, 1981","volume":"18","author":"Guzman","year":"1984","journal-title":"Bull Pan Am Health Organ"},{"key":"R16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4269\/ajtmh.1995.52.241","article-title":"Partial nucleotide and amino acid sequences of the envelope and the envelope\/nonstructural protein-1 gene junction of four dengue-2 virus strains isolated during the 1981 Cuban epidemic","volume":"52","author":"Guzman","year":"1995","journal-title":"Am J Trop Med Hyg"},{"key":"R17","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1126\/science.239.4839.476","article-title":"Pathogenesis of dengue: challenges to molecular 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