Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1007996
Title: Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C
Authors: Lim, X.-N.
Shan, C.
Marzinek, J.K.
Dong, H.
Ng, T.S. 
Ooi, J.S.G. 
Fibriansah, G. 
Wang, J. 
Verma, C.S. 
Bond, P.J.
Shi, P.-Y.
Lok, S.-M. 
Issue Date: 2019
Publisher: Public Library of Science
Citation: Lim, X.-N., Shan, C., Marzinek, J.K., Dong, H., Ng, T.S., Ooi, J.S.G., Fibriansah, G., Wang, J., Verma, C.S., Bond, P.J., Shi, P.-Y., Lok, S.-M. (2019). Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C. PLoS Pathogens 15 (9) : e1007996. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1007996
Rights: Attribution 4.0 International
Abstract: The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to "bumpy" surfaced morphology when the temperature is switched from 29°C at 37°C. Here we identified five envelope (E) protein residues different between two alternative passage history DENV2 NGC strains exhibiting smooth or bumpy surface morphologies. Several mutations performed on the smooth DENV2 infectious clone destabilized the surface, as observed by cryoEM. Molecular dynamics simulations demonstrated how chemically subtle substitution at various positions destabilized dimeric interactions between E proteins. In contrast, three out of four DENV2 clinical isolates showed a smooth surface morphology at 37°C, and only at high fever temperature (40°C) did they become "bumpy". These results imply vaccines should contain particles representing both morphologies. For prophylactic and therapeutic treatments, this study also informs on which types of antibodies should be used at different stages of an infection, i.e., those that bind to monomeric E proteins on the bumpy surface or across multiple E proteins on the smooth surfaced virus. Copyright © 2019 Lim et al.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/212503
ISSN: 1553-7366
DOI: 10.1371/journal.ppat.1007996
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_ppat_1007996.pdf7.18 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

12
checked on May 14, 2022

Page view(s)

40
checked on May 12, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons