Influenza A virus hemagglutinin glycoprotein (HA)

The **Influenza A virus hemagglutinin glycoprotein** (HA) is the most abundant surface glycoprotein on the Influenza A virion, comprising a homotrimer of membrane-anchored polypeptides. It is the primary mediator of viral infectivity, enabling the attachment of the virus to sialic acid-containing receptors on the surface of host cells in the upper respiratory tract, followed by internalization via endocytosis[1][2][4][6]. In the endosome, HA undergoes a pH-induced conformational change leading to the fusion of the viral envelope with the endosomal membrane, allowing the viral genome to enter the host cytoplasm[1][4][6]. HA is also the main antigen recognized by the immune system. It is the principal target of neutralizing antibodies, and its antigenic variability via mutation (antigenic drift and shift) enables immune evasion and is responsible for recurrent seasonal epidemics and occasional pandemics[4][6]. HA is synthesized as an inactive precursor (HA0), which must be proteolytically cleaved into HA1 and HA2 subunits for activation; HA1 constructs the receptor-binding "head", while HA2 forms the stalk and fusion machinery[1][5][6]. Therapeutically, HA is a validated target for vaccine design and for monoclonal antibody therapy, although no small-molecule drugs currently target HA in clinical practice[4][1]. Because of its antigenic diversity, developing a universal influenza vaccine remains an ongoing challenge. Neutralizing monoclonal antibodies targeting conserved HA regions, particularly the stalk, are under investigation for broad-spectrum influenza prevention and therapy[4][1].

Other names

Influenza hemagglutininHAInfluenza virus hemagglutininHemagglutinin glycoproteinInfluenza A hemagglutinin

Neutralizing antibodies block receptor-binding (inhibit viral attachment)[1][4]. Antibodies binding the stalk domain inhibit membrane fusion between the viral and host cell membranes[4]. Fusion inhibitors (experimental) prevent conformational change necessary for fusion[4].