Fig 1.
An EBOV particle is shown with key viral proteins highlighted, including: the viral glycoprotein, matrix proteins (VP40, VP24), and viral ribonucleoprotein complex (RNA-dependent RNA polymerase, VP30, VP35, nucleoprotein, and RNA).
Fig 2.
Structure of the EBOV glycoprotein (GP).
(Top) Each monomer of GP consists of a GP1 and GP2 heterodimer associated via a disulfide bond. GP1 contains the receptor binding domain (RBD), protected by a glycan cap and a mucin like domain (MLD) at the apex of the structure. The RBD interacts with the endosomal receptor Niemann-Pick C1 (NPC1) upon proteolytic processing of GP1 that removes the glycan cap and MLD. The fusion loop, which imbeds in the target membrane during fusion, is part of the GP2 monomer, but remains hidden in the mature pre-fusion GP trimer. (Bottom)The GP trimer consists of three GP1/2 heterodimers (shown in different shades) that associate through several GP1/GP2 and GP2/GP2 interactions.
Fig 3.
(A) Cell surface receptors bind EBOV particles through interactions with either virion-associated phosphatidylserine or viral glycoprotein glycans. (B) Virus is internalized through ruffling of the plasma membrane and macropinocytosis. (C) During trafficking through endosomes, the EBOV glycoprotein is cleaved by proteases that remove the mucin-like domain (MLD) and glycan cap, exposing the receptor binding domain (RBD). Shown is a stepwise removal of those sequences, although in the cell these cleavage events may occur concurrently. (D) The RBD interacts with NPC1 in the late endosome/lysosome. (E) Binding of the NPC1 C-loop by the glycoprotein is followed by one or more triggers that release the fusion loop, allowing for its insertion into the target membrane. Subsequent transition of the EBOV GP into a six helix bundle results in the host and viral membranes being brought together, leading to fusion. (F) Release of the viral nucleoprotein into the cytoplasm prior to the initiation of virus replication.