1.G.14 The Influenza Virus Hemagglutinin/Fusion Pore-forming Protein (Influenza-H/FPP) Family
Hemagglutinin (HA) is the viral protein that facilitates the entry of influenza viruses into host cells. This protein controls two critical aspects of entry: virus binding and membrane fusion. In order for HA to carry out these functions, it must first undergo a priming step, proteolytic cleavage, which renders it fusion competent. Membrane fusion commences from inside the endosome after a drop in lumenal pH and an ensuing conformational change in HA that leads to the hemifusion of the outer membrane leaflets of the virus and endosome, the formation of a stalk between them, followed by pore formation (Hamilton et al. 2012).
Viral glycoproteins, such as influenza hemagglutinin (HA) and human immunodeficiency virus gp41, are anchored by a single TMS to the viral envelope membrane. The fusion peptides (FP) of the glycoproteins insert into the host membrane and initiate membrane fusion. The FP-TMS pair increases the lipid order at all positions, which has a greater lipid ordering effect than the each of the FP or TMD alone, and this effect reaches deeper into the membranes. This interaction may provide driving force in different stages of membrane fusion: initialization, transition from hemifusion stalk to transmembrane contact, and fusion pore formation (Lai and Freed 2015).