Specific Single or Double Proline Substitutions in the “Spring-loaded” Coiled-Coil Region of the Influenza Hemagglutinin Impair or Abolish Membrane Fusion Activity

Qiao, Hui; Pelletier, Sandra L.; Hoffman, Lucas; Hacker, Jill; Armstrong, R. Todd; White, Judith M.

A ll enveloped viruses use a membrane fusion event to introduce their infectious genomes into cells. Whereas some enveloped viruses, such as influenza, fuse at low pH in endosomes, others, such as HIV, do so at neutral pH (Hernandez et al., 1996) . Recent work has led to the hypothesis that viral membrane fusion proteins are activated by "spring-loaded" conformational changes. According to the hypothesis, the spring-loaded conformational change occurs in response to a fusion trigger, for example low endosomal pH, and leads to the formation of an extended ␣ -helical coiled-coil that propels the previously buried fusion peptide to the target bilayer. Interaction of the fusion peptide with the target bilayer would then initiate membrane fusion (Carr and Kim, 1993; Bullough et al., 1994; Hughson, 1995; Hernandez et al., 1996) .