Influenza virus hemagglutinin stem region (HA stem) (HA stem)

The influenza virus hemagglutinin (HA) stem region is a highly conserved domain of the primary surface glycoprotein responsible for viral entry into host cells (Nature, 2018). While the HA head region undergoes frequent antigenic drift, the stem region (primarily composed of the HA2 subunit) remains relatively invariant across diverse influenza A and B strains (Science, 2015). This conservation makes it a critical target for the development of universal influenza vaccines and broadly neutralizing antibodies (bnAbs) (Cell, 2019). Biologically, the stem region mediates the fusion of the viral envelope with the host endosomal membrane through a pH-triggered conformational change (PNAS, 2016). Therapeutic agents targeting this region, such as monoclonal antibodies like MEDI8852 or small molecules like Umifenovir, function by stabilizing the pre-fusion conformation (The Lancet Infectious Diseases, 2020). By sterically hindering the fusion machinery, these drugs prevent the release of the viral genome into the host cytoplasm (Nature Communications, 2019). This mechanism effectively neutralizes the infection across multiple viral subtypes, offering a broader range of protection than traditional vaccines (Journal of Virology, 2018).

Other names

Hemagglutinin stalk regionHA2 subunitInfluenza HA stem domainConserved stem regionHemagglutinin fusion region

The primary mechanism involves binding to the conserved stem region to sterically block the pH-induced conformational change required for membrane fusion, thereby preventing the release of the viral genome into the host cell (Nature Communications, 2019).