Influenza A virus H7N9 hemagglutinin stalk domain (H7N9 HA stalk)

The Influenza A H7N9 hemagglutinin (HA) stalk domain is a critical structural component of the viral surface glycoprotein responsible for mediating host cell entry (UniProt A0A0K2H7N0). Unlike the highly variable globular head domain (HA1), the stalk domain, primarily composed of the HA2 subunit, is relatively conserved across various influenza subtypes, making it a primary target for the development of universal influenza vaccines and broadly neutralizing antibodies (Corts et al., 2021, J. Virol.). Its main biological function is to facilitate the fusion of the viral envelope with the host endosomal membrane through a pH-triggered conformational change (Harrison, 2015, Curr Top Microbiol Immunol). In the context of H7N9, a highly pathogenic avian influenza strain, targeting this domain is essential for preventing severe respiratory infection and systemic spread (NIH, 2023). Therapeutic agents, such as monoclonal antibodies like MEDI8852, bind to the stalk to lock it in its pre-fusion state, thereby neutralizing the virus's ability to infect cells (Kallewaard et al., 2016, Cell).

Other names

HA2 subunitHemagglutinin stem domainH7N9 HA stemInfluenza A virus H7N9 HA2

Broadly neutralizing antibodies (bnAbs) target the HA stalk to inhibit the pH-dependent conformational change required for membrane fusion, effectively blocking viral entry into the host cell (PubMed: 27424871). Some antibodies also mediate protection through Fc-receptor-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) (PubMed: 30531946).