Influenza virus hemagglutinin stem (HA stem)

Influenza virus hemagglutinin (HA) is the primary surface glycoprotein of the influenza virus, responsible for both host cell receptor binding and the fusion of viral and endosomal membranes. The HA protein consists of a highly variable globular head domain and a more conserved stem (or stalk) domain. The HA stem/interface has become a major focus for the development of universal influenza vaccines and therapeutics because its sequence is highly conserved across diverse viral strains and subtypes. Drugs targeting this region, such as small molecules like JNJ4796 and broadly neutralizing antibodies like MEDI8852, act by binding to the stem and stabilizing the prefusion conformation of the HA trimer. This stabilization prevents the irreversible, low-pH-triggered conformational change necessary for membrane fusion, thereby blocking the release of the viral genome into the host cell. Clinical efforts aim to use these stem-targeted agents to provide broad protection against seasonal antigenic drift and potential pandemic shifts that bypass the immunity provided by traditional head-directed vaccines.

Other names

Hemagglutinin stalkHA stalkHA2 subunitHA head-stem interfaceHemagglutinin fusion domain

Inhibition of viral-host membrane fusion by binding to the conserved stem region and stabilizing the prefusion conformation of hemagglutinin, thereby blocking the pH-induced conformational changes required for viral entry.