Influenza A virus H10 hemagglutinin stem domain (H10 HA stem)

The Influenza A virus H10 hemagglutinin (HA) stem domain is a highly conserved region of the HA surface glycoprotein, which is essential for the entry of the influenza virus into host cells (NIH, 2020). Unlike the immunodominant globular head domain that undergoes rapid antigenic drift, the stem domain—primarily composed of the HA2 subunit and parts of the HA1 subunit—remains relatively stable across different strains and subtypes within Group 2 influenza viruses, including H10 (TandfOnline, 2023). Its primary biological function is to mediate the fusion of the viral envelope with the host endosomal membrane through a pH-triggered conformational change (NIH, 2015). This conservation makes the H10 HA stem domain a critical target for the development of broadly neutralizing antibodies (bnAbs) and universal influenza vaccines (NIH, 2018). Therapeutic agents targeting this domain, such as the monoclonal antibody MEDI8852, work by binding to the stem and preventing the structural rearrangements necessary for membrane fusion, thereby neutralizing the virus (NIH, 2020). Additionally, some stem-binding antibodies can inhibit viral egress by sterically hindering the activity of the nearby neuraminidase protein (NIH, 2015).

Other names

H10 hemagglutinin stalk domainH10 HA2 domainH10 HA stemInfluenza A H10 stalkH10 hemagglutinin stem

Inhibition of the pH-induced conformational change of the hemagglutinin stem, which prevents the fusion of the viral envelope with the host cell endosomal membrane (NIH, 2020). Some antibodies also provide protection through antibody-dependent cellular cytotoxicity (ADCC) or by sterically hindering neuraminidase activity to prevent viral egress (NIH, 2015).