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Comparative Characterization of Dengue Virus Serotype 2 Isolates from a South Pacific Epidemic Sweep.

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Title:Comparative Characterization of Dengue Virus Serotype 2 Isolates from a South Pacific Epidemic Sweep.
Authors:Steel, Argon
Contributors:Biomedical Sciences (Tropical Medicine) (department)
Date Issued:May 2017
Publisher:University of Hawaiʻi at Mānoa
Abstract:The four serotypes of dengue virus (DENV-1, DENV-2, DENV-3 and DENV-4) cause a wide
spectrum of clinical disease, ranging from febrile illnesses to life-threatening hemorrhagic
fever. Worldwide incidence has increased alarmingly to where DENV is now the most
common mosquito-borne viral disease in the world. However, understanding the mechanisms
by which DENV causes disease remains elusive, due both to the complexity of vector-host
transmission and the lack of effective in vitro and animal models with which to test
mechanisms of pathogenesis. Our previous work, in which we carried out phylogenetic
analysis of an epidemic sweep of DENV-2 among South Pacific islands that occurred in the
early 1970s, suggests that strain variation might have a significant impact on epidemic
severity. Specifically, DENV-2 isolates from an outbreak on the island of Tonga – whose
epidemiology was notable for being distinctly attenuated compared with outbreaks on all other
affected islands – were found to have three unique amino acid substitutions in the prM, NS2A
and NS4A gene regions that distinguished them from all other DENV-2 isolates. Therefore,
based on the hypothesis that changes in the DENV genome can lead to variations in disease
severity and epidemic potential between different DENV strains, this study explores the
relationship between genetic changes in DENV-2 epidemic strains and their phenotypic effects
using in vitro models. Phenotypic differences between DENV-2 isolates from the entire South
Pacific sweep were measured on the basis of viral productivity (i.e., viral titer and replication
rate or rate of virus production per cell) in both human and mosquito cells. In addition, the
specific mutations characterizing the Tonga synapomorphies suggested additional
measurements to examine the proportion of infectious virions and possibly the viral effects on
host-immune responses.
Description:Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017.
URI:http://hdl.handle.net/10125/62204
Rights:All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections: Ph.D. - Biomedical Sciences (Tropical Medicine)


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