Influenza A virus hemagglutinin group 1 stem domain (HA group 1 stem)

The Influenza A hemagglutinin (HA) group 1 stem domain is a highly conserved structural region of the HA surface glycoprotein found in Group 1 influenza A viruses, which include subtypes such as H1, H2, H5, and H9 (Ekiert et al., 2009, Science). While the HA globular head mediates attachment to host sialic acid receptors and is subject to frequent antigenic drift, the stem domain is responsible for the critical step of membrane fusion (Bullough et al., 1994, Nature). Upon endocytosis, the acidic environment of the endosome triggers a massive conformational rearrangement in the stem that brings the viral and host membranes together, allowing the viral genome to enter the cytoplasm (Harrison, 2008, Nature Reviews Microbiology). Because of its high sequence conservation across different strains, the stem domain is the primary target for "universal" influenza vaccine strategies and broadly neutralizing monoclonal antibodies (bnAbs) like CR6261 and MEDI8852 (Corti et al., 2011, Science). These therapeutic agents typically function by binding to the stem and physically locking the protein in its pre-fusion state, preventing the pH-induced change required for infection (Kallewaard et al., 2016, Cell). Targeting this domain offers a promising avenue for providing broad-spectrum protection against both seasonal and emerging pandemic influenza threats.

Other names

Hemagglutinin stalk domainHA stemHA2 subunit (primary component)Influenza A group 1 HA stalkHemagglutinin stem region

Binding to the conserved stem region prevents the pH-triggered conformational change of hemagglutinin, thereby blocking the fusion of the viral envelope with the host endosomal membrane and preventing the release of the viral genome into the host cell cytosol.