Structural study of the relationship between the rate of membrane fusion and the ability of the fusion peptide of influenza virus to perturb bilayers.

The amino-terminal segment of the HA2 protein of influenza virus (fusion peptide) has been identified as an important region for membrane fusion. The wild type virus can fuse to membranes more rapidly at pH 5 than at pH 7.4. It has been demonstrated that there is a relationship between the ability of the peptide to promote the formation of inverted phases and the fusogenicity of the intact virus. In this work, we use small-angle X-ray diffraction to study the mechanism of the structural effect of the peptide, at different pHs, on lipid systems characterized by each having a different spontaneous radius of curvature. The overall results show that the action of the peptide on the polymorphism of the lipid systems investigated is strongly pH-dependent. In particular, a rapid formation of cubic phases at pH 5.0 is observed in the presence of this fusion peptide. The ability of the fusion peptide to promote cubic phases exhibits the same dependence on the pH as does the fusogenicity of the intact virus. It is proposed that the peptide promotes cubic phases at pH 5.0 by changing the kinetics of the lamellar to inverted phase transitions.