Relationship between the infectivity of influenza virus and the ability of its fusion peptide to perturb bilayers.

The amino terminal segment of the HA2 protein of influenza virus has been identified as an important region for membrane fusion. We demonstrate that there is an association between the ability of model peptides corresponding to this region of the HA2 protein to promote the formation of inverted phases and the fusogenicity of the intact virus. The wild type virus can fuse to membranes at pH 5 but not at pH 7.4. We show that the fusion peptide of the wild type virus lowers the bilayer to hexagonal phase transition temperature of dipalmitoleoylphosphatidylethanolamine at pH 5 but at pH 7.4 it raises this transition temperature. In addition it has been shown that site specific mutagenesis resulting in the substitution of Gly with Glu leads to a loss of viral infectivity. These same amino acid substitutions in the viral fusion peptide result in the peptide no longer being able to lower the bilayer to hexagonal phase transition temperature, even at acidic pH. The wild type fusion peptide promotes the formation of structures which give rise to isotropic 31P NMR spectra at pH 5.0 but not at pH 7.4. The two altered sequences of the fusion peptide, corresponding to the Glu to Gly mutations, do not promote isotropic 31P NMR signals at acidic pH. These results indicate that the fusogenicity of influenza virus is dependent, in part, on the ability of the amino terminal region of HA2 to disrupt stable bilayer packing and to induce curvature strain corresponding to inverted phase structures.