Influenza A virus hemagglutinin (HA) stem region (HA stem)

The Influenza A virus hemagglutinin (HA) stem region is a highly conserved structural domain of the viral surface glycoprotein, essential for mediating the fusion between the viral envelope and the host cell endosomal membrane (Corti et al., Science, 2011). While the globular head of HA frequently mutates to evade the immune system, the stem region remains relatively invariant across both Group 1 (e.g., H1, H5) and Group 2 (e.g., H3, H7) influenza A subtypes, making it a primary target for universal vaccine and therapeutic design (Dreyfus et al., Science, 2012). Upon exposure to the acidic environment of the endosome, the HA stem undergoes a massive conformational rearrangement that pulls the viral and host membranes together. Therapeutic agents, particularly broadly neutralizing antibodies (bnAbs) like MEDI8852 and FI6v3, bind to this region and physically lock the protein in its pre-fusion state, thereby preventing viral entry and infection (Kallewaard et al., Cell, 2016). This target is currently the focus of intensive research to develop long-lasting, cross-protective countermeasures against seasonal and pandemic influenza threats (Impagliazzo et al., Science, 2015). The development of small molecules like JNJ-4796 also demonstrates the feasibility of targeting this region with non-biologic inhibitors (van Dongen et al., Science, 2019).

Other names

Hemagglutinin stalkHA stalkHA2 subunitConserved HA stem regionInfluenza A HA stalk

Binding to the conserved stem region of hemagglutinin to inhibit the pH-induced conformational change required for viral-host membrane fusion.