VISUALIZATION OF FUSION ACTIVATION IN THE SEMLIKI FOREST VIRUS SPIKE

Background: Viral spike proteins such as those of Semliki Forest virus (SFV) undergo a conformational change triggered by low pH which resul ts in the fusion of the viral envelope with cellular membranes. The vi ral spike precursor of SFV is insensitive to low pH, and hence is fusi on incompetent, until it is proteolytically cleaved to give the fusion competent mature form. Results: Three-dimensional image reconstructio ns from cryo-electron micrographs were used to compare the virion stru cture of wild-type SFV with that of a mutant SFV in which cleavage of the spike precursor had been blocked. Upon maturation to the fusion co mpetent form, the spike undergoes a conformational change in which cop ies of the polypeptide containing the fusion sequence (E1) move from p eripheral to lateral positions bringing them closer together. Conclusi ons: This first visualization of the maturation of a viral spike prote in complex suggests a mechanism for the conformational change which co ntrols the fusion process.