Conformational changes in intact dengue virus reveal serotype-specific expansion

Xin-Xiang Lim, Arun Chandramohan, Xin Ying Elisa Lim, Nirmalya Bag, Kamal Kant Sharma, Melissa Wirawan, Thorsten Wohland, Shee-Mei Lok and Ganesh S. Anand ()
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Xin-Xiang Lim: National University of Singapore
Arun Chandramohan: National University of Singapore
Xin Ying Elisa Lim: Duke-National University of Singapore Graduate Medical School
Nirmalya Bag: National University of Singapore
Kamal Kant Sharma: National University of Singapore
Melissa Wirawan: Duke-National University of Singapore Graduate Medical School
Thorsten Wohland: National University of Singapore
Shee-Mei Lok: National University of Singapore
Ganesh S. Anand: National University of Singapore

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C (associated with host entry), despite high sequence and structural homology among the four known serotypes. The basis for this differential expansion across strains and serotypes is unknown and necessitates mapping of the dynamics of dengue whole viral particles to describe their coordinated motions and conformational changes when exposed to host-like environments. Here we capture the dynamics of intact viral particles of two serotypes, DENV1 and DENV2, by amide hydrogen/deuterium exchange mass spectrometry (HDXMS) and time resolved Förster Resonance Energy Transfer. Our results show temperature-dependent dynamics hotspots on DENV2 and DENV1 particles with DENV1 showing expansion at 40 °C but not at 37 °C. HDXMS measurement of virion dynamics in solution offers a powerful approach to identify potential epitopes, map virus-antibody complex structure and dynamics, and test effects of multiple host-specific perturbations on viruses and virus-antibody complexes.

Date: 2017
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DOI: 10.1038/ncomms14339

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