Conformational changes in intact dengue virus reveal serotype-specific expansion
Xin-Xiang Lim1, Arun Chandramohan1, Xin Ying Elisa Lim2
1Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
Nature Communications
|February 11, 2017
Summary
Dengue virus serotype 2 (DENV2) expands structurally at 37°C, while DENV1 expands at 40°C. This study maps viral particle dynamics, revealing temperature-dependent expansion hotspots for DENV1 and DENV2.
Area of Science:
- Virology
- Structural Biology
- Biophysics
Background:
- Dengue virus serotypes share high homology but exhibit differential structural dynamics.
- Understanding these dynamics is crucial for host entry mechanisms and vaccine development.
Purpose of the Study:
- To map the dynamics and conformational changes of intact dengue virus serotypes 1 and 2 (DENV1 and DENV2) in host-like environments.
- To investigate the basis for differential structural expansion across dengue virus serotypes.
Main Methods:
- Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) to measure virion dynamics in solution.
- Time-resolved Förster Resonance Energy Transfer (TR-FRET) to capture viral particle dynamics.
Main Results:
- Identified temperature-dependent dynamics hotspots on both DENV1 and DENV2 viral particles.
- Observed structural expansion in DENV2 at 37°C and in DENV1 at 40°C, but not at 37°C.
- Demonstrated the utility of HDXMS for studying virion dynamics in solution.
Conclusions:
- Dengue virus serotypes exhibit distinct temperature-dependent structural dynamics.
- HDXMS is a powerful tool for identifying viral epitopes and mapping virus-antibody interactions.
- These findings provide insights into dengue virus host entry and potential therapeutic targets.
