Influenza A virus H5 hemagglutinin subunit HA2 (HA2)

The H5 hemagglutinin subunit HA2 is the membrane-anchored component of the influenza A virus hemagglutinin (HA) protein, specifically within the H5 subtype [10, 12]. It is produced alongside the HA1 subunit through the proteolytic cleavage of the precursor HA0 protein [4, 13]. While HA1 facilitates viral attachment to host sialic acid receptors, HA2 is responsible for the subsequent fusion of the viral envelope with the host endosomal membrane [1, 12]. This fusion process is triggered by the acidic environment of the endosome, which causes HA2 to undergo a dramatic conformational rearrangement that inserts its N-terminal fusion peptide into the host membrane [2, 8]. Due to its high sequence conservation across various influenza strains, HA2 is a major focus for the development of universal vaccines and broadly neutralizing antibodies [9, 11]. Therapeutic agents targeting HA2, including small molecules like Umifenovir and various monoclonal antibodies such as CR6261, function by stabilizing the prefusion structure and blocking the mechanical transition necessary for viral entry [5, 11].

Other names

HA2 subunitHemagglutinin stalk domainFusion subunitHA2 glycopolypeptideHA2 fusion peptide

Inhibition of viral-host membrane fusion by stabilizing the prefusion conformation of hemagglutinin and preventing the low-pH-induced structural rearrangement [5, 11].