Infectivity of dengue virus serotypes 1 and 2 is correlated to E protein intrinsic dynamics but not to envelope conformations

Abstract

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 [A] 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.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC=\"FIGDIR/small/303560_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (58K):\norg.highwire.dtl.DTLVardef@aac485org.highwire.dtl.DTLVardef@14c318corg.highwire.dtl.DTLVardef@1490d27org.highwire.dtl.DTLVardef@feb06a_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract/ cover Figure\n\nC_FIG