THESIS DEFENSE — PUBLIC SEMINAR: HOST RESPONSE TO FLAVIVIRAL INFECTION

Start Date & Time: 
Friday, 20 October, 2017 - 10:00
End Date & Time: 
Friday, 20 October, 2017 - 11:00
Venue: 

Venue: Amphitheatre, Level 2,  Duke-NUS

Speaker: 
Speaker Details: 

CHAN YUEN YUE CANDICE
IBM PhD PROGRAM (INTAKE 2013)

Synopsis: 

Exposure to pathogenic flaviviruses is necessary but inadquate 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, whether host responses also determine whether an infection is clinically overt or asympatomatic has yet to be elucidated. To examine the early molecular 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 early up-regulation of genes involved in TOLL-receptor signalling and innate immune respnses at day 1 post-vaccination 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.

Thesis Advisor: Prof. Ooi Eng Eong