Hemagglutinin subunit HA2 (HA2) (HA2)

The Hemagglutinin subunit HA2 of the A/Indonesia/05/2005 (H5N1) influenza virus is a critical component of the viral envelope glycoprotein responsible for mediating host cell entry [UniProt Q207Z6]. While the HA1 subunit facilitates initial binding to sialic acid receptors, the HA2 subunit (the stalk or stem region) undergoes a dramatic pH-dependent conformational change within the endosome to trigger membrane fusion [Ekiert et al., 2009]. This fusion process allows the viral ribonucleoproteins to enter the host cytoplasm, initiating infection [Sui et al., 2009]. Because the HA2 stalk region is significantly more conserved across different influenza strains than the highly mutable HA1 head, it has become a primary target for the development of universal influenza vaccines and broadly neutralizing antibodies [Throsby et al., 2008]. Therapeutic agents targeting this region, such as monoclonal antibodies CR6261 or MEDI8852, typically function by stabilizing the pre-fusion conformation and preventing the structural rearrangements necessary for fusion [Dreyfus et al., 2012]. Targeting the HA2 stem is particularly vital for pandemic preparedness against highly pathogenic avian influenza strains like H5N1 [Lappala et al., 2018]. Small molecule inhibitors like Umifenovir also interact with the HA stem to block the fusion transition [Kadam & Wilson, 2017]. Research into this target focuses on overcoming the immunodominance of the HA1 head to elicit a robust protective response against the stalk [Impagliazzo et al., 2015].

Other names

HA2 stemHemagglutinin stalk regionHA2 fusion peptideInfluenza A virus H5N1 HA2H5N1 stalkA/Indonesia/05/2005 HA2

Stabilization of the pre-fusion conformation of hemagglutinin to prevent the pH-induced structural rearrangements required for membrane fusion and viral entry [Ekiert et al., 2009].