TCDB is operated by the Saier Lab Bioinformatics Group

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).

References associated with 1.G.14 family:

Desai, T.M., M. Marin, C.R. Chin, G. Savidis, A.L. Brass, and G.B. Melikyan. (2014). IFITM3 Restricts Influenza A Virus Entry by Blocking the Formation of Fusion Pores following Virus-Endosome Hemifusion. PLoS Pathog 10: e1004048. 24699674
Hamilton, B.S., G.R. Whittaker, and S. Daniel. (2012). Influenza virus-mediated membrane fusion: determinants of hemagglutinin fusogenic activity and experimental approaches for assessing virus fusion. Viruses 4: 1144-1168. 22852045
Lai, A.L. and J.H. Freed. (2015). The Interaction between Influenza HA Fusion Peptide and Transmembrane Domain Affects Membrane Structure. Biophys. J. 109: 2523-2536. 26682811
Wang, M., K. Ludwig, C. Böttcher, and M. Veit. (2016). The role of stearate attachment to the hemagglutinin-esterase-fusion glycoprotein HEF of influenza C virus. Cell Microbiol 18: 692-704. 26518983