Visualization of fusion activation in the Semliki Forest virus spike.

Viral spike proteins such as those of Semliki Forest virus (SFV) undergo a conformational change triggered by low pH which results in the fusion of the viral envelope with cellular membranes. The viral spike precursor of SFV is insensitive to low pH, and hence is fusion incompetent, until it is proteolytically cleaved to give the fusion competent mature form. Three-dimensional image reconstructions from cryo-electron micrographs were used to compare the virion structure 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 competent form, the spike undergoes a conformational change in which copies of the polypeptide containing the fusion sequence (E1) move from peripheral to lateral positions bringing them closer together. This first visualization of the maturation of a viral spike protein complex suggests a mechanism for the conformational change which controls the fusion process.