Influenza A virus hemagglutinin stalk region (HA stalk)

The Influenza A virus hemagglutinin (HA) stalk region is a critical, highly conserved component of the virus's primary surface glycoprotein, which is essential for host cell entry. While the globular head of the HA protein undergoes frequent antigenic drift, the stalk region remains relatively stable across diverse influenza A subtypes, including H1 and H5 (PMID: 22878502). Biologically, the stalk functions as a molecular spring that, upon exposure to the acidic environment of the endosome, undergoes a dramatic conformational change to facilitate the fusion of the viral and host membranes (UniProt: P03452). This fusion process is vital for the release of the viral ribonucleoprotein complex into the host cytoplasm. Therapeutic strategies targeting the HA stalk, such as broadly neutralizing monoclonal antibodies like MedI8852 and universal vaccine candidates, aim to block this conformational shift or sterically hinder the fusion machinery (PMID: 26912702). Consequently, the HA stalk is a focal point for developing broad-spectrum countermeasures against both seasonal and pandemic influenza threats (PMID: 23303906).

Other names

Hemagglutinin stem regionHA2 subunitConserved stalk domainHA stalk domainHemagglutinin fusion domain

Binding to the conserved stalk region prevents the pH-triggered conformational change required for the fusion of the viral envelope with the host endosomal membrane, thereby blocking viral entry into the host cell.