Lim Xin Ying Elisa

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gmslxye@nus.edu.sg


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DUKE-NUS MEDICAL SCHOOL
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    Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations
    (CELL PRESS, 2019-04-02) Sharma, Kamal Kant; Lim, Xin-Xiang; Tantirimudalige, Sarala Neomi; Gupta, Anjali; Marzinek, Jan K; Holdbrook, Daniel; Lim, Xin Ying Elisa; Bond, Peter J; Anand, Ganesh S; Wohland, Thorsten; Dr Kamal Kant Sharma; BIOLOGICAL SCIENCES; DUKE-NUS MEDICAL SCHOOL
    Dengue is a mosquito-borne virus with dire health and economic impacts. Dengue is responsible for an estimated 390 million infections per year, with dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also in strains of this serotype that temperature-dependent large-scale morphological changes, termed “breathing,” have been observed. Although the structure of these morphologies has been solved to 3.5-Å resolution, the dynamics of the viral envelope are unknown. Here, we combine fluorescence and mass spectrometry with molecular dynamics simulations to provide insights into DENV2 (NGC strain) structural dynamics in comparison with DENV1 (PVP 159). We observe hitherto unseen conformational changes and structural dynamics of the DENV2 envelope that are influenced by both temperature and divalent cations. Our results show that for DENV2 and DENV1 the intrinsic dynamics, but not the specific morphologies, are correlated with viral infectivity.
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    Antibody affinity versus dengue morphology influences neutralization
    (Public Library of Science, 2021-02-23) Fibriansah, Guntur; Lim, Elisa X. Y.; Marzinek, Jan K.; Ng, Thiam-Seng; Tan, Joanne L.; Huber, Roland G.; Lim, Xin-Ni; Chew, Valerie S. Y.; Kostyuchenko, Victor A.; Shi, Jian; Anand, Ganesh S.; Bond, Peter J.; Crowe, James E.; Lok, Shee-Mei; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); BIOLOGICAL SCIENCES; DUKE-NUS MEDICAL SCHOOL
    Different strains within a dengue serotype (DENV1-4) can have smooth, or “bumpy” surface morphologies with different antigenic characteristics at average body temperature (37C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes. Copyright: © 2021 Fibriansah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.