HA2

HA2 is the C-terminal subunit of the influenza virus hemagglutinin (HA) protein, produced when the HA0 precursor is cleaved by host proteases into HA1 and HA2. This cleavage is a prerequisite for viral infectivity. The HA2 subunit contains the conserved fusion peptide at its N-terminus, which becomes exposed in the acidic environment of the endosome and drives the merging of viral and endosomal membranes, allowing viral RNA to enter the host cell.

Structurally, HA2 includes regions known as the heptad repeats (HR1 and HR2) that form a six-helix bundle during the postfusion state. A transmembrane domain near the C-terminus anchors HA2 to the viral envelope. The conformational changes of HA2 from a prefusion to a postfusion form are central to the membrane fusion step of viral entry.

HA2 is more conserved across influenza subtypes than the HA1 subunit, contributing to its prominence as a target for broadly neutralizing antibodies and for antiviral strategies aimed at fusion inhibition. While antibodies that broadly recognize HA2 can neutralize diverse influenza strains, the immune response is often more focused on HA1, making HA2 an area of ongoing research for universal vaccine design and therapeutic development.

In summary, HA2 is the fusion-facilitating subunit of influenza hemagglutinin, essential for viral entry and a key focus in efforts to understand influenza evolution, immunity, and the pursuit of broadly protective interventions.