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 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.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Arun
authors.initials: A
authors.lastname: Chandramohan
authors.affiliation: Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Xin Ying Elisa
authors.initials: XY
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Nirmalya
authors.initials: N
authors.lastname: Bag
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Kamal Kant
authors.initials: KK
authors.lastname: Sharma
authors.affiliation: Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Melissa
authors.initials: M
authors.lastname: Wirawan
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.|Department of Chemistry, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117557, Singapore.
authors.forename: Thorsten
authors.identifier: 0000-0002-0148-4321
authors.initials: T
authors.lastname: Wohland
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.|Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Shee-Mei
authors.initials: SM
authors.lastname: Lok
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Anand
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D041961:Deuterium Exchange Measurement; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D065288:Serogroup; D013696:Temperature; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
chemical_list: D000914:Antibodies, Viral; D014759:Viral Envelope Proteins