Structure-Based Mutations in the Herpes Simplex Virus 1 Glycoprotein B Ectodomain Arm Impart a Slow-Entry Phenotype

Fan, Qing; Kopp, Sarah J.; Connolly, Sarah A.; Longnecker, Richard

Destabilizing the postfusion form of gB also could impact fusion by altering the thermodynamic equilibrium between the prefusion and postfusion forms in the gB population (Fig. 10C) . Although reversibility of the gB conformational change has not been demonstrated, the refolding of rhabdovirus fusion protein G (another class III fusion protein) from a prefusion to a postfusion conformation is reversible (46) (47) (48) . If the prefusion and postfusion conformations of rhabdovirus G exist in equilibrium, mutations that destabilize the postfusion form could decrease fusion capacity by shifting the equilibrium toward the prefusion state. The gB 3A mutations may destabilize the postfusion gB conformation by decreasing the affinity of the arm for the coil and thereby push the equilibrium within the gB population toward the prefusion state.