1.G.12 The Avian Leukosis Virus gp95 Fusion Protein (ALV-gp95) Family
Retroviruses rely on low pH to activate their fusion proteins that merge the viral envelope with an endosomal membrane, releasing the viral nucleocapsid into the cytosol (Jha et al., 2011). The fusion process involves a relatively stable hemifusion-like intermediate that precedes fusion pore opening. EnvA (gp95) mediates entry through alternative receptor isoforms and intermediates of virus-endosome fusion (Jha et al., 2011).
The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis (Apellániz et al. 2014). Firstly, the VFP sequence must achieve a set of native interactions required for (meta) stable folding within the globular ectodomains of the glycoprotein complexes. Secondly, at the onset of the fusion process, these complexes get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Apellániz et al. 2014 reviewed different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions.