Immune suppressive activity of the influenza fusion peptide

•An immune suppressive domain is identified in the fusion peptide of influenza viruses.•This domain is active when presented in a dimeric but not in a monomeric form.•This domain is the most conserved part of the fusion protein of influenza viruses.

Immune suppressive domains have been identified in retro and filoviral fusion proteins. Such domains constitute small peptide motifs that are evolutionarily very well preserved within each group. We here test the hypothesis that such preservation reflects a dual selection pressure for both immune suppression and membrane fusion activity in influenza viruses for which no immune suppressive peptide motifs have been identified. We identified a conserved motif in the fusion peptide of influenza hemagglutinin as a candidate for an immune suppressive domain using comparative and phylogenetic analysis. This peptide was indeed found to exhibit immune suppressive activity in several in vitro assays. Similar to the previously reported peptides from retro and filoviruses the influenza peptide had immune suppressive activity when presented as a dimer but not as a monomer.