Influenza hemagglutinin stem region (HA stem)

The influenza hemagglutinin stem region is a highly conserved domain at the base of the hemagglutinin (HA) protein, protruding from the surface of the influenza virus. Unlike the immunodominant globular head, the stem fulfills essential biological functions: it anchors HA to the viral membrane and mediates the fusion of the viral and host cellular membranes during infection, a process triggered by low pH in the endosome[1][6][7]. The stem domain is structurally characterized by alpha-helical coils spanning the trimer interface, and contains the fusion peptide required for membrane merger[6]. The HA stem is a validated therapeutic target, underlying both broadly neutralizing antibody therapies and universal vaccine strategies; its high sequence conservation makes it suitable for cross-subtype targeting[7][8]. Mutations in the stem region modulate HA stability and therefore influence viral transmission, host range, and pathogenicity[2][3][4]. Promising interventions include rationally stabilized stem immunogens and monoclonal antibodies that inhibit fusion, offering potential to prevent or treat a broad spectrum of influenza infections[5][7][8].

Other names

Hemagglutinin stemHA stem domainHemagglutinin fusion domain

Inhibition of viral entry by blocking membrane fusion[7][8] Stabilization of prefusion HA conformation to prevent structural changes required for infection[5][7][8] Targeting highly conserved epitopes to neutralize multiple influenza subtypes[7][8]