title: Insights into the molecular evolution of Dengue virus type 4 in Puerto Rico over two decades of emergence.
abstract: Dengue has emerged globally as a major human health problem since the 1950s and is now the most important arboviral disease of humans, infecting nearly 400 million people annually. While some cases are asymptomatic, others can develop a febrile illness (dengue fever) or even progress to severe and fatal dengue. Dengue is caused by any of 4 closely related but distinct viruses, known as Dengue virus serotype 1 to 4 (DENV-1 to DENV-4) which are maintained in endemic transmission to humans in large urban centers of the tropics by Aedes mosquitoes. Since the early 1960s, Puerto Rico, a major metropolitan center in the Caribbean, has experienced increasingly larger and clinically more severe epidemics following the introduction of all four dengue serotypes. The first dengue hemorrhagic fever epidemic in 1986, and a particularly severe outbreak in 1998 were dominated by novel DENV-4 strains that evolved in Puerto Rico, replacing earlier strains and spreading throughout the region. Sequence characterization of 54 complete DENV-4 genomes and their comparative evolution against 74 previously published viral sequences from the region over several decades shows that DENV-4 strains from these periods were genetically distinct based on unique changes in the envelope and non-structural genes. Their replacement of earlier strains in Puerto Rico progressed rapidly, suggesting that strong natural selection played a role in their fixation. This study confirms that DENVs evolve through rapid lineage turnover driven in part by natural selection and genetic drift.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA.
authors.forename: Estelle
authors.initials: E
authors.lastname: Martin
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan, PR, USA.
authors.forename: Maritza
authors.initials: M
authors.lastname: Chirivella
authors.affiliation: Department of Biology, De La Salle University, Manila, Philippines.
authors.forename: Juliene K G
authors.initials: JKG
authors.lastname: Co
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan, PR, USA.
authors.forename: Gilberto A
authors.initials: GA
authors.lastname: Santiago
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Duane J
authors.initials: DJ
authors.lastname: Gubler
authors.affiliation: Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan, PR, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Muñoz-Jordán
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, USA; Department of Microbiology, California Academy of Sciences, San Francisco, CA, USA. Electronic address: sbennett@calacademy.org.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Bennett
mesh_terms: D003715:Dengue / Q000453:epidemiology / Q000821:virology*; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology; D011647:Puerto Rico / Q000453:epidemiology; D012367:RNA, Viral / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics
chemical_list: D012367:RNA, Viral; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins
keywords: Dengue virus; Emergence; Evolution; Lineage turnover; Natural selection