Tang Choon Kit

Email Address
gmstchk@nus.edu.sg


Organizational Units
OrgUnit Logo
Organizational Unit
DUKE-NUS MEDICAL SCHOOL
faculty
OrgUnit Logo
Organizational Unit

Filters

2016 - 20172
Reset filters

Settings

Citations

Publication Search Results

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Publication
    Dengue virus activates cGAS through the release of mitochondrial DNA
    (2017) Sun B.; Sundström K.B.; Chew J.J.; Bist P.; Gan E.S.; Tan H.C.; Goh K.C.; Chawla T.; Tang C.K.; Ooi E.E.; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOL
    Cyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS. Innate immune responses triggered by cGAMP contribute to limiting the spread of DENV to adjacent uninfected cells through contact dependent gap junctions. Our result thus supports the notion that RNA virus indirectly activates a DNA-specific innate immune signaling pathway and highlights the breadth of the cGAS-induced antiviral response. © 2017 The Author(s).
  • No Thumbnail Available
    Publication
    Molecular determinants of plaque size as an indicator of dengue virus attenuation
    (2016) Goh K.C.M.; Tang C.K.; Norton D.C.; Gan E.S.; Tan H.C.; Sun B.; Syenina A.; Yousuf A.; Ong X.M.; Kamaraj U.S.; Cheung Y.B.; Gubler D.J.; Davidson A.; St John A.L.; Sessions O.M.; Ooi E.E.; DUKE-NUS MEDICAL SCHOOL
    The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.