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 b een identified as an important region for membrane fusion. We demonstr ate that there is an association between the ability of model peptides corresponding to this region of the HA2 protein to promote the format ion of inverted phases and the fusogenicity of the intact virus. The w ild type virus can fuse to membranes at pH 5 but not at pH 7.4. We sho w that the fusion peptide of the wild type virus lowers the bilayer to hexagonal phase transition temperature of dipalmitoleoylphosphatidyle thanolamine at pH 5 but at pH 7.4 it raises this transition temperatur e. In addition it has been shown that site specific mutagenesis result ing in the substitution of Gly with Glu leads to a loss of viral infec tivity. These same amino acid substitutions in the viral fusion peptid e result in the peptide no longer being able to lower the bilayer to h exagonal phase transition temperature, even at acidic pH. The wild typ e fusion peptide promotes the formation of structures which give rise to isotropic P-31 NMR spectra at pH 5.0 but not at pH 7.4. The two alt ered sequences of the fusion peptide, corresponding to the Glu to Gly mutations, do not promote isotropic P-31 NMR signals at acidic pH. The se results indicate that the fusogenicity of influenza virus is depend ent, in part, on the ability of the amino terminal region of HA2 to di srupt stable bilayer packing and to induce curvature strain correspond ing to inverted phase structures. (C) 1994 Academic Press, Inc.