Influenza A H1N1 hemagglutinin stem (HA stem)

The Influenza A H1N1 hemagglutinin (HA) stem is a highly conserved domain of the major surface glycoprotein of the influenza virus, playing a pivotal role in viral entry [1, 5]. While the HA head domain is subject to frequent antigenic drift, the stem region (primarily composed of the HA2 subunit and parts of HA1) remains relatively stable across diverse H1N1 strains and even other Group 1 influenza subtypes [3, 4]. Biologically, the HA stem mediates the fusion of the viral envelope with the host endosomal membrane, a process triggered by low pH that induces a massive, irreversible conformational change in the protein [5, 8]. This fusion is essential for releasing the viral ribonucleoprotein complexes into the host cell cytoplasm to initiate replication [11, 14]. Therapeutic agents targeting the HA stem, including broadly neutralizing antibodies like MEDI8852 and CR6261, as well as small molecules like JNJ4796, function by binding to a conserved hydrophobic groove and locking the HA in its pre-fusion state [4, 6, 17]. This prevents the structural rearrangements necessary for membrane fusion and effectively neutralizes the virus [9, 15]. Furthermore, the HA stem is the primary focus of "universal" influenza vaccine strategies, such as the H1ssF nanoparticle vaccine, which aim to elicit broad-spectrum immunity by redirecting the immune response away from the immunodominant head domain [2, 18].

Other names

Hemagglutinin stalkHA stalkHA2 domainHA stem regionConserved HA stem

Inhibition of pH-induced conformational change of the hemagglutinin protein, thereby blocking the fusion of the viral envelope with the host cell endosomal membrane [4, 6, 10].