National University of Singapore (NUS) - Department of Biological Sciences; Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute
National University of Singapore (NUS) - Department of Biological Sciences; Agency for Science, Technology and Research (A*STAR) - Bioinformatics Institute
Dengue is a mosquito-borne virus with dire health and economic impact. Dengue is responsible for an estimated ~390 million infections per year, with Dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also for strains of this serotype that temperature-dependent large scale morphological changes, termed as “breathing”, have been observed. Although, the structure of these morphologies has been solved to 3.5 Å resolution, the dynamics of the viral envelope are unknown. Here, we combine fluorescence and mass spectrometry and molecular dynamics simulations to provide insights into DENV2 structural dynamics in comparison to DENV1. We observe hitherto unseen conformational changes and structural dynamics of the DENV2 envelope that are influenced by both temperature and divalent cations. Our results show that for DENV2 and DENV1 the intrinsic dynamics but not the specific morphologies are correlated to viral infectivity.
sharma, kamal kant and Lim, Xin-Xiang and Tantirimudalige, Sarala Neomi and Gupta, Anjali and Marzinek, Jan K. and Holdbrook, Daniel and Lim, Xin Ying Elisa and Bond, Peter J. and Anand, Ganesh S. and Wohland, Thorsten, Infectivity of Dengue Virus Serotypes 1 and 2 is Correlated to E Protein Intrinsic Dynamics But Not to Envelope Conformations (June 2018). Available at SSRN: https://ssrn.com/abstract=3193413 or http://dx.doi.org/10.2139/ssrn.3193413
This version of the paper has not been formally peer reviewed.
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