Infectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations

Kamal Kant Sharma, Xin Xiang Lim, Sarala Neomi Tantirimudalige, Anjali Gupta, Jan K. Marzinek, Daniel Holdbrook, Xin Ying Elisa Lim, Peter J. Bond, Ganesh S. Anand, Thorsten Wohland

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Dengue is a mosquito-borne virus with dire health and economic impacts. 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 in strains of this serotype that temperature-dependent large-scale morphological changes, termed “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 with molecular dynamics simulations to provide insights into DENV2 (NGC strain) structural dynamics in comparison with DENV1 (PVP 159). 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 with viral infectivity.

Original languageEnglish (US)
Pages (from-to)618-630.e4
JournalStructure
Volume27
Issue number4
DOIs
StatePublished - Apr 2 2019

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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