Influenza hemagglutinin head–stem interface (HA head–stem interface)

The **influenza hemagglutinin head–stem interface** is a structural region within the trimeric hemagglutinin (HA) glycoprotein of influenza viruses, at the junction between the globular head domains (containing the receptor binding site) and the membrane-proximal stem (also called stalk) domain[1][4][5][6][9]. HA is the primary antigen and fusion protein mediating virus attachment and entry into host cells via binding to sialic acid-containing receptors on the cell surface and subsequent membrane fusion in the endosome. The HA head–stem interface is highly conserved, and a recently described target of broadly protective human antibodies, some of which can disrupt trimer stability or block viral fusion, conferring cross-strain protection[3][6][8][10]. This epitope is not surface-exposed in all HA conformations but becomes accessible during certain states; it is a current focus of universal influenza vaccine and therapeutic antibody development. Most therapeutic efforts target either the variable head or more conserved stem domains, but the head–stem interface represents a new, promising "site of vulnerability"[3][6][10]. No small-molecule drugs are known to target this interface, but multiple monoclonal antibodies that bind this region are in preclinical or clinical development[3][6][10]. **Note:** “Influenza hemagglutinin head–stem interface” is a recently validated and promising therapeutic target, but not a classical receptor, enzyme, or transporter in the conventional sense; it is a discrete structural epitope on a viral entry protein. The canonical molecule is “influenza hemagglutinin”, and the head–stem interface specifies the targeted region[1][3][6][10].

Other names

Influenza HA head–stem interfaceHemagglutinin trimer interfaceHA trimer head interfaceHemagglutinin head domain interfaceHemagglutinin stemInfluenza virus trimer interface

Antibodies binding the head–stem interface can disrupt hemagglutinin trimer stability Fc-dependent immune effector functions such as infected cell killing Blockage of conformational changes or virus–host membrane fusion