Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/137722
Title: DETERMINANTS OF SYMPTOMATIC FLAVIVIRAL INFECTION
Authors: CHAN YUEN YUE CANDICE
Keywords: dengue, flavivirus, live attenuated vaccine, immunology, host-pathogen interactions, pathogenicity
Issue Date: 28-Sep-2017
Source: CHAN YUEN YUE CANDICE (2017-09-28). DETERMINANTS OF SYMPTOMATIC FLAVIVIRAL INFECTION. ScholarBank@NUS Repository.
Abstract: Exposure to pathogenic flaviviruses is necessary but inadequate for development of symptomatic disease, as majority of flaviviral infections are clinically silent. The host response during early infection is an important determinant of disease progression. However, how host responses determine whether an infection is clinically overt or asympatomatic has yet to be elucidated. To examine the events during pre-symptomatic stage of flavivirus infection, I analysed the systemic adverse events in human volunteers following yellow fever live-attenuated vaccination as a surrogate for symptomatic infection. Collectively, the data indicates that there was no association between YF vaccine viraemia and symptomatic infection. Instead, early up-regulation of genes involved in TOLL-receptor signalling and innate immune responses at day 1 post-vaccination, before detectable viraemia, were positively correlated with development of symptoms commonly reported in acute febrile illness, the onset of which was at day 6 post-vaccination. Furthermore, as the ratio of symptomatic and asymptomatic infection of dengue is influenced by whether the infection is primary or secondary, this thesis also examined how infection through antibody-dependent enhancement (ADE) pathway shapes the early host responses to infection. Experimental findings in primary human monocytes showed that the route of entry also determines the early host transcriptional response, both qualitatively and quantitatively. Collectively, findings from this thesis suggest that early host responses, which is shaped at least in part by the route of virus entry and are expressed prior to detectable viraemia, determine whether a flaviviral infection is symptomatic or asymptomatic.
URI: http://scholarbank.nus.edu.sg/handle/10635/137722
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Thesis_FINAL_Chan Yuen Yue Candice.pdf35.36 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

10
checked on Jan 14, 2018

Download(s)

3
checked on Jan 14, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.