Figure 7. Zaire ebolavirus glycoprotein-mediated entryEbolavirus is thought to enter cells through an endocytic mechanism.

(A) Initially, the metastable, prefusion Zaire ebolavirus GP may bind lectins [71] or an unidentified attachment factor at the cell surface (green ovals) via the mucin-like domains (grey spheres) or other sites on GP. (B) Subsequently, ebolavirus is internalized and trafficked to the endosome. Lectins may or may not remain bound to GP, depending on the nature of the individual lectin. In the endosome, host cathepsins cleave GP to remove the glycan cap and mucin-like domain, yielding an approximately 19-kDa GP₁ core, disulfide bonded to GP₂. (C) The newly exposed surface may allow either tighter binding to a receptor trafficked from the cell surface or binding to an alternate molecule in the endosome. Binding of this molecule, or perhaps further cathepsin cleavage, could then trigger conformational changes in the GP₂ fusion subunit. (D) Structural rearrangements in GP₂ allow HR1 to form a single 44-residue helix and position the IFL for insertion into the host-endosomal membrane. Upon insertion in the host membrane, the IFL adopts a 3₁₀ helix. This is the extended prehairpin intermediate. (E) Based on studies with the influenza virus, more than one trimer of GP₂ may be required to complete the membrane fusion process. (F) The HR2 and MPER regions swing from the viral membrane towards the host membrane and HR1. Initial fold-back of the HR2 onto HR1 distorts the virus and host-cell bilayers and brings the two membranes into contact to form a hemifusion stalk. (G) The hemifusion stalk opens up to form the fusion pore and the low energy, postfusion 6HB is formed when three HR2 helices pack into the HR1 trimeric bundle.

6HB: Six helix bundle; CatL/B: Cathepsin L/B; GP: Glycoprotein; HR: Heptad repeat region; IFL: Internal fusion loop; MPER: Membrane-proximal external region; TACE: TNF-α-converting enzyme; TM: Transmembrane domain.

Adapted from [34,51].