Hypothetical model of Bunyavirus:cell fusion. Steps in the entry process of Bunyaviruses can be extrapolated from current models of class II viral fusion protein-mediated virion cell fusion. Panel A. The Bunyavirus glycoproteins Gn and Gc are modeled according to SIN virion structure analyses by Zhang et al. . Based on limited similarities with Alphavirus E2 proteins (Table 3), Gn is depicted as the receptor-binding protein of Bunyaviruses. Certain Bunyaviruses may encode other membrane-associated proteins that interact with the fusion peptide or other regions of Gc. Panel B: Receptor-binding triggers uptake of Bunyavirus virion by endocytosis. Panel C: Acidification of the endocytic vesicle occurs via the action of proton transporters and may initiate Gn and Gc dissociation. Panel D: bending at the flexible "hinge" region beween domains I and II permits Gc trimer formation and insertion of the fusion peptide into the endosomal vesicle membrane. Panel D' Alternatively, Gc trimer formation may involve the rotation of domain III and a rearrangement (twist) of domain II as shown for SFV E1, DEN E and TBEV E [11,33,54]. Panel E: As previously proposed [11,33,54] the formation of more extensive Gc contacts in the trimers and stem regions may release of energy for distortion of the endosomal and viral membranes resulting in formation of "nipple-like" projections. Panel E': Alternatively, aa sequences of Gc that form a track with the ability to interface with bilayer membranes (Fig. 2, black), may facilitate mixing of the endosomal and viral membranes. Panel F: Formation of further trimer contacts and hemifusion. Hemifusion may not occur in the D' and E' pathway. Panel G: Formation of the "fusion pore" and entry of the ribonucleoprotein (RNP) segments. Modified from models and concepts proposed in references 9-12.