James Crowe
Faculty Member
Last active: 3/31/2020

Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody.

Wirawan M, Fibriansah G, Marzinek JK, Lim XX, Ng TS, Sim AYL, Zhang Q, Kostyuchenko VA, Shi J, Smith SA, Verma CS, Anand G, Crowe JE, Bond PJ, Lok SM
Structure. 2019 27 (2): 253-267.e8

PMID: 30471923 · PMCID: PMC6365167 · DOI:10.1016/j.str.2018.10.009

Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop. Here, we determined cryoelectron microscopy (cryo-EM) maps of the immDENV:anti-prM complex at different pH values, mimicking the extracellular (pH 8.0) or endosomal (pH 5.0) environments. At pH 5.0, there are two structural classes with fewer antibodies bound than at pH 8.0. These classes may represent different maturation states. Molecular simulations, together with the measured high-affinity pr:antibody interaction (versus the weak pr:E interaction) and also the low pH cryo-EM structures, suggest how antibody:pr complex can dislodge from the E protein at low pH. This exposes the E protein fusion loop enhancing virus interaction with endosomes.

Copyright © 2018 Elsevier Ltd. All rights reserved.

MeSH Terms (13)

Animals Antibodies, Viral Cell Line Cryoelectron Microscopy Dengue Virus Endosomes Humans Hydrogen-Ion Concentration Immunoglobulin Fab Fragments Models, Molecular THP-1 Cells Viral Proteins Virus Attachment

Connections (1)

This publication is referenced by other Labnodes entities: