“Structure of dengue virus as determined by cryo-electron microscopy and image reconstruction techniques”

Professor Richard Kuhn

Biological Sciences

Purdue University

Flaviviruses are important human pathogens and are represented by dengue, yellow fever and West Nile virus. The first structure of a flavivirus, that of dengue, has been determined by using a combination of cryo-electron microscopy and fitting of the known structure of glycoprotein E into the electron density map to a resolution of ~ 11 Å. The virus core, within a lipid bilayer, has a less ordered structure than the external, icosahedral scaffold of 90 glycoprotein E dimers. The three E monomers per icosahedral asymmetric unit do not have quasi-equivalent symmetric environments. In addition, structures of immature dengue and yellow fever virus particles were determined to 16 Å and 25 Å resolution, respectively, by cryo-electron microscopy and image reconstruction techniques. The closely similar structures show 60, icosahedrally-organized, trimeric spikes on the particle surface. Each spike consists of three prM:E heterodimers, where E is an envelope glycoprotein and prM is the precursor to the membrane protein, M. The pre‑peptide components of the prM proteins in each spike cover the fusion peptides at the distal ends of the E glycoproteins. Each heterodimer is associated with an E and a prM transmembrane density. These transmembrane densities represent either an EE or prMprM antiparallel coiled coil by which each protein spans the membrane twice, leaving the carboxy terminus of each protein on the exterior of the viral membrane, consistent with the predicted membrane-spanning domains of the unprocessed polyprotein. These structures have important implications for flavivirus biology and provide insight into the arrangement of membrane proteins with lipid bilayers.