Influenza A virus hemagglutinin (HA)

Influenza A virus hemagglutinin (HA) is a homotrimeric surface glycoprotein essential for the initiation of viral infection (UniProt: P03435). It functions by binding to sialic acid residues on the surface of host epithelial cells and subsequently mediating the fusion of the viral envelope with the endosomal membrane at low pH. HA is the primary component of seasonal influenza vaccines, serving as the major target for neutralizing antibodies that provide immunity (CDC, 2023). The protein consists of two subunits: HA1, which contains the receptor-binding site and is subject to frequent antigenic drift, and HA2, which contains the fusion machinery and is more conserved across strains. Because of its central role in viral entry and its high immunogenicity, HA remains the focal point for vaccine development and the design of broad-spectrum antiviral therapies, including monoclonal antibodies and fusion inhibitors. Therapeutic strategies often target the conserved stalk region to elicit universal protection against multiple influenza subtypes (PubMed: 30639332).

Other names

HemagglutininHA proteinInfluenza hemagglutininH1H3Surface glycoproteinHA1/HA2

Vaccines containing HA antigens induce the host immune system to produce neutralizing antibodies that bind to the HA globular head or stalk, thereby preventing viral attachment to host sialic acid receptors or inhibiting the pH-dependent conformational change required for membrane fusion (CDC, 2023; PubMed: 30639332). Small molecule inhibitors like umifenovir directly bind to the HA protein to stabilize the prefusion state and prevent the fusion process (PubMed: 31131313).