Influenza A virus hemagglutinin stalk domain (HA stalk)

The Influenza A virus hemagglutinin (HA) stalk domain is a highly conserved region of the primary surface glycoprotein responsible for viral entry into host cells (PubMed: 29305462). Unlike the immunodominant globular head, which undergoes rapid antigenic drift, the stalk domain remains relatively stable across diverse influenza subtypes, making it a premier target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) (PubMed: 30559449). Biologically, the stalk domain undergoes a dramatic pH-triggered conformational change within the endosome, facilitating the fusion of the viral envelope with the host cell membrane (UniProt: P03435). Therapeutic strategies targeting this domain typically aim to lock the HA protein in its pre-fusion state or sterically hinder the fusion machinery, thereby neutralizing the virus (PubMed: 22675084). Clinical development in this area focuses on providing broad-spectrum protection against seasonal and pandemic influenza strains, addressing the limitations of current strain-specific vaccines (ClinicalTrials.gov: NCT02514083). Small molecules like Umifenovir also interact with this domain to prevent the structural rearrangements necessary for fusion (PubMed: 30639257). The stalk domain is also a target for antibody-dependent cellular cytotoxicity (ADCC), which helps the immune system clear infected cells (PubMed: 24336207).

Other names

Hemagglutinin stem domainHA stemHA2 domainInfluenza A virus HA stalk

Inhibition of pH-induced conformational change and membrane fusion