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; Ganesh S. Anand

doi:10.1038/ncomms14339

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, Ganesh S. Anand

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56 Scopus citations

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.

Original language	English (US)
Article number	14339
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms14339
State	Published - Feb 10 2017

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Conformational changes in intact dengue virus reveal serotype-specific expansion",

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 F{\"o}rster 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.",

author = "Lim, {Xin Xiang} and Arun Chandramohan and Lim, {Xin Ying Elisa} and Nirmalya Bag and Sharma, {Kamal Kant} and Melissa Wirawan and Thorsten Wohland and Lok, {Shee Mei} and Anand, {Ganesh S.}",

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doi = "10.1038/ncomms14339",

language = "English (US)",

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T1 - Conformational changes in intact dengue virus reveal serotype-specific expansion

AU - Lim, Xin Xiang

AU - Chandramohan, Arun

AU - Lim, Xin Ying Elisa

AU - Bag, Nirmalya

AU - Sharma, Kamal Kant

AU - Wirawan, Melissa

AU - Wohland, Thorsten

AU - Lok, Shee Mei

AU - Anand, Ganesh S.

PY - 2017/2/10

Y1 - 2017/2/10

N2 - 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.

AB - 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.

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Conformational changes in intact dengue virus reveal serotype-specific expansion

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