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.
Highlights
Dengue virus serotype 2 (DENV2) alone undergoes structural expansion at 37 °C, despite high sequence and structural homology among the four known serotypes
The high sequence and structural homology of DENV1 and DENV2 at 28 °C does not provide any apparent correlation between sequence/structural assembly13,14 and the observed differential temperature-dependent expansion in DENV2 and DENV1 in solution
In order to capture temperature-induced changes in the two dengue serotypes: Purified DENV1 (PVP 159) and DENV2 (NGC), intact, infectious viral particles were equilibrated at 28, 37 or 40 °C as specified, for 30 min and deuterium exchange was initiated by 10-fold dilution in deuterated buffer to result in a final deuterium oxide concentration of 90%
Summary
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. Cryo-EM structures of viral particles describe the viral envelope and symmetry at 28 and 37 °C, they only represent a single stable endpoint state and offer limited predictive insights into its large-scale temperature and other host-specific perturbation-dependent transitions. The high sequence and structural homology of DENV1 and DENV2 at 28 °C does not provide any apparent correlation between sequence/structural assembly and the observed differential temperature-dependent expansion in DENV2 and DENV1 in solution This necessitates a thermodynamic description of the whole viral particle in solution at separate temperatures
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
