Influenza A virus hemagglutinin group 1 stalk domain (HA stalk (Group 1))

The Influenza A virus hemagglutinin (HA) group 1 stalk domain is a critical structural component of the HA protein, which is the major surface glycoprotein of the influenza virus [Ekiert et al., 2009, Science]. While the HA protein is divided into the immunodominant, highly variable globular head and the more conserved stalk (or stem) region, the group 1 stalk is specifically shared among subtypes such as H1, H2, H5, and H9 [Cyrus et al., 2020, Vaccines]. Its primary biological function is to facilitate membrane fusion between the viral envelope and the host cell endosome following a pH-triggered conformational change [Harrison, 2008, Nature Reviews Microbiology]. Because the stalk domain is less prone to antigenic drift than the head, it has become a focal point for universal influenza vaccine strategies and broadly neutralizing antibodies [Krammer & Palese, 2013, Nature Reviews Drug Discovery]. Therapeutic agents targeting this domain, such as the monoclonal antibody CR6261, work by binding to a hydrophobic pocket in the stalk and preventing the structural rearrangement required for viral entry [Throsby et al., 2008, PLoS ONE].

Other names

Hemagglutinin stem domainHA2 subunitGroup 1 HA stemConserved stalk regionHA stalk region

Binding to the conserved stalk region prevents the pH-triggered conformational change of hemagglutinin required for fusion between the viral envelope and the host endosomal membrane, thereby neutralizing the virus [Ekiert et al., 2009, Science].