Hypothetical models of gB refolding energetics. Although gB refolding likely progresses through several intermediate conformations, only the prefusion and postfusion conformation energy states are depicted. The hypothetical impact of the gB 3A mutations on these states is shown in red. Comparisons of energy of activation (EA) are shown as vertical lines. (A) The 3A mutations may stabilize the gB prefusion conformation, thereby increasing the EA required to trigger gB and reducing gB fusion capacity. (B) The 3A mutations may increase the EA required to achieve an intermediate conformation of gB, such as a prehairpin intermediate, thereby reducing the gB fusion capacity. (C) By decreasing the affinity of the arm for the coil, the 3A mutations may destabilize the postfusion gB, thereby reducing the EA required to move from a postfusion to a prefusion conformation. At equilibrium, this would increase the proportion of the gB population in a prefusion state.