Physiological temperatures reduce dimerization of dengue and Zika virus recombinant envelope proteins.

摘要: The spread of dengue (DENV) and Zika virus (ZIKV) is a major public health concern. primary target antibodies that neutralize DENV ZIKV the envelope (E) glycoprotein, there interest in using soluble recombinant E (sRecE) proteins as subunit vaccines. However, most potent neutralizing against recognize epitopes on virion surface span two or more proteins. Therefore, to create effective vaccines, presentation these quaternary may be necessary. sRecE from crystallize native-like dimers, but studies solution suggest dimers are marginally stable. To better understand challenges associated with creating stable we characterized thermostability three serotypes, DENV2-4. All four irreversibly unfolded at moderate temperatures (46-53 °C). At 23 °C low micromolar concentrations, DENV2 were primarily dimeric, DENV3-4 monomeric, whereas 37 °C, all predominantly monomeric. We further show dissociation constant for dimerization very temperature-sensitive, ranging <1 μm 25 50 41 due large exothermic enthalpy binding -79 kcal/mol. also found epitope antibody DENV2-4 reduced °C. Our observation physiological temperature highlights need stabilizing dimer part its development vaccine.