Hemagglutinin - Stalk Region (HA (stalk region))

The hemagglutinin stalk region is a structural subdomain of the influenza virus hemagglutinin (HA) protein, located at the base of the HA trimer beneath the globular head. It is primarily formed by portions of both HA1 and HA2 subunits but is especially defined by the long α-helical coils of HA2, which play a crucial role in mediating the dramatic conformational changes required for viral and host membrane fusion during entry[6][3][7]. The stalk acts as a scaffold for trimer assembly, supports the head domain, and is the primary target of broadly neutralizing antibodies, making it highly relevant to universal influenza vaccine strategies. While the HA head is immunodominant yet highly variable, the stalk is structurally conserved across influenza subtypes, particularly in the functional fusion peptide and coiled-coil regions[7][3][6]. Antibodies that target the stalk can block membrane fusion and neutralize diverse influenza strains, driving significant interest in therapeutics and vaccine development targeting this domain. Stalk regions in hemagglutinins from other viruses (like paramyxovirus or measles) play similar roles in fusion and viral entry[1][4].

Other names

Influenza hemagglutinin stalk regionHA stalk domainHemagglutinin stem (for influenza)HA stem region

Inhibition of conformational changes needed for membrane fusion (for antibodies and fusion inhibitors)[7][3]; Viral neutralization via steric hindrance of stalk-mediated fusion[7][3]; Prevention of low pH-induced transition required for virus entry[7][3]