Influenza A virus hemagglutinin stem region (HA stem) (HA stem)

The Influenza A virus hemagglutinin (HA) stem region is a highly conserved domain of the HA surface glycoprotein, primarily composed of the HA2 subunit and portions of the HA1 subunit [1]. Unlike the highly variable globular head region, the stem region remains relatively constant across different influenza strains and subtypes, making it a prime target for the development of universal influenza vaccines and broad-spectrum therapeutics [2]. Its primary biological role is to mediate the fusion of the viral envelope with the host cell's endosomal membrane during viral entry [1]. This process is triggered by the acidic environment of the endosome, which induces a massive, irreversible conformational change in the stem region, often described as a spring-loaded mechanism [3]. Therapeutic agents, such as broadly neutralizing antibodies (bnAbs) and certain small molecules, bind to this conserved pocket to stabilize the pre-fusion state and physically block the fusion machinery [4]. By inhibiting this critical step of the viral life cycle, these drugs can provide protection against a wide range of influenza A viruses, including both seasonal and pandemic-potential strains [3]. Sources: [1] PubMed: 28100931; [2] Science: 10.1126/science.aac7263; [3] Science: 10.1126/science.1208530; [4] Science: 10.1126/science.aar6221.

Other names

Hemagglutinin stalk regionHA2 subunitConserved stem domainHA stalk

Binding to the conserved stem region prevents the pH-triggered conformational change of the hemagglutinin protein, thereby blocking the fusion of the viral envelope with the host endosomal membrane and preventing viral genome release into the cytoplasm.