Influenza A virus hemagglutinin stem (HA stem)

The Influenza A virus hemagglutinin (HA) stem is a critical component of the viral entry machinery, primarily composed of the HA2 subunit and the proximal portions of the HA1 subunit. Unlike the immunodominant globular head of the HA protein, which undergoes frequent antigenic drift, the stem region is highly conserved across various influenza A subtypes, including both Group 1 and Group 2 viruses (Ekiert et al., Science 2009). Its primary biological role is to mediate the fusion between the viral envelope and the host endosomal membrane through a dramatic pH-dependent conformational change triggered upon endocytosis (UniProt P03435). This conservation makes the HA stem a premier target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs). Therapeutic agents targeting this region, such as the monoclonal antibody MEDI8852 or small molecules like JNJ-4796, function by binding to a hydrophobic pocket in the stem and locking the protein in its pre-fusion state (Kallewaard et al., Cell 2016). By preventing the structural rearrangement necessary for membrane fusion, these therapies can neutralize a wide range of influenza strains, offering potential protection against both seasonal drift and pandemic shift (NIH NIAID, Universal Influenza Vaccine Research).

Other names

Hemagglutinin stalkHA stalkHA2 subunitConserved HA stem domainInfluenza HA stem region

Inhibition of the pH-triggered conformational change of hemagglutinin, which prevents the fusion of the viral envelope with the host endosomal membrane, thereby blocking viral entry into the host cell.