Sylvatic dengue: evolution, emergence, and impact on human health

dc.contributor.advisorScott C. Weaveren_US
dc.contributor.committeeMemberStanley J. Watowichen_US
dc.contributor.committeeMemberRobert B. Teshen_US
dc.contributor.committeeMemberPeter W. Masonen_US
dc.contributor.committeeMemberKathryn A. Hanleyen_US
dc.contributor.committeeMemberD. Mark Estesen_US
dc.creatorNikolaos Vasilakisen_US
dc.date.accessioned2011-12-20T16:05:45Z
dc.date.available2008-06-17en_US
dc.date.available2011-12-20T16:05:45Z
dc.date.created2007-12-21en_US
dc.date.issued2007-10-24en_US
dc.description.abstractDengue viruses (DENV) are the most important arboviral pathogens in tropical and subtropical regions throughout the world. Transmission includes a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes, and an urban, endemic/epidemic cycle between Aedes aegypti, a mosquito with larval development in peridomestic water containers, and human reservoir hosts. All 4 serotypes of endemic DENV evolved independently from ancestral sylvatic viruses and have become both ecologically and evolutionarily distinct. The independent evolutionary events that resulted in the emergence of DENV were facilitated by the expansion of DENV progenitors’ host range in Asia to new vectors and hosts that occurred gradually over a period of several hundred years. Emerging viral pathogens often become human pathogens by changing their host range from another vertebrate organism. This study assessed the likelihood of current sylvatic DENV-2 strains to emerge into the human transmission cycle by investigating the factors that facilitate their emergence. My analysis of sylvatic and endemic DENV-2 strains’ ability to replicate in two surrogate human model hosts, determined that adaptation to humans is probably not a necessary component of sylvatic dengue emergence. Then, through an analysis of several sylvatic DENV-2, I demonstrated that both endemic and sylvatic DENV-2 share similar rates of evolutionary change and patterns of natural selection. These findings imply that the potential of future DENV re-emergence from the sylvatic cycle is high. Subsequently, phylogenetic analysis of virus genomes isolated from febrile patients in Nigeria during DENV-2 activity, demonstrated that unrecognized outbreaks of sylvatic DENV-2 in humans are possible. However, their re-emergence into the endemic cycle would be limited by homotypic immunity mediated by virus neutralizing antibodies.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-12212007-070652en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/299
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectsylvaticen_US
dc.subjectphylogeneticsen_US
dc.subjectevolutionen_US
dc.subjectemergenceen_US
dc.subjectDengue virusen_US
dc.subjectarbovirologyen_US
dc.titleSylvatic dengue: evolution, emergence, and impact on human healthen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentExperimental Pathologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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