[en] The entry of enveloped viruses into target cells requires the fusion between the viral
envelope and the target cell membrane. In the case of many viruses like HIV, SIV
and BLV, the fusion is mediated by class 1 fusion glycoproteins located on the viral
envelope. These fusion glycoproteins contain a region at their N-terminal extremity
called the “fusion peptide”, which interact with the target membrane. Many
mutagenesis studies showed that this region is required for mediating membrane
fusion [1]. Moreover, synthetic peptides corresponding to the fusion peptide of
many glycoproteins induce membrane fusion in vitro. Despite the large number of
studies on synthetic fusion peptides, the region necessary and sufficient to induce
optimal membrane fusion is not known. To determine this minimal fusion peptide,
we used the “tilted peptide” theory. According to this theory, a helical peptide
inserting obliquely into membranes induces fusion [2]. Moreover, the more tilted the
peptide is, the more important the fusion is. Then, we postulate that the minimal
fusion peptide corresponds to the shortest helical fragment able to insert into the
membrane with an angle close to 45°. This peptide was predicted using the
IMPALA algorithm, which allow to predict peptide-membrane interactions [3].
Fusogenicity of this peptide was then assessed in liposome lipid-mixing and leakage
assays and compared to the fusogenicity of smaller and longer peptides to check the
validity of the prediction. This methodology was used to determine successfully the
minimal fusion peptide of three viruses, HIV, SIV and BLV.
