Hemagglutinin protein stem (HA stem)

The Hemagglutinin (HA) protein stem is a highly conserved region of the primary surface glycoprotein of the influenza virus, consisting primarily of the HA2 subunit and portions of the HA1 subunit [2, 17]. Unlike the rapidly mutating globular head domain, the stem region remains relatively stable across various influenza strains and subtypes, making it a critical target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) [7, 13, 19]. Biologically, the HA stem facilitates the fusion of the viral envelope with the host endosomal membrane through a series of irreversible conformational changes triggered by the low-pH environment of the endosome [15, 17, 22]. In its role in disease, HA is the primary antigen responsible for viral entry and host infection, contributing to both seasonal epidemics and global pandemics [1, 2, 7]. Drugs and antibodies targeting the HA stem typically function by physically blocking these conformational rearrangements, thereby preventing the release of the viral genome into the host cell cytoplasm [3, 14, 16]. Additionally, some stem-targeted therapies may inhibit the proteolytic cleavage of the HA precursor (HA0) or promote the clearance of infected cells via Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity (ADCC) [10, 18, 21].

Other names

Hemagglutinin stalkHA stalkHemagglutinin stem regionHemagglutinin stalk domainHA2 subunit stem

Inhibition of pH-induced conformational changes to block viral-host membrane fusion; inhibition of HA0 proteolytic cleavage; recruitment of Fc-mediated effector functions like antibody-dependent cellular cytotoxicity (ADCC).