Hemagglutinin of influenza A virus subtype H1 (HA)

Hemagglutinin of influenza A virus subtype H1 (HA) is a homotrimeric transmembrane glycoprotein essential for viral entry into host cells. It consists of HA1 and HA2 subunits, where the globular HA1 head domain binds sialic acid-containing receptors on respiratory epithelial cells, enabling viral attachment, while the HA2 stem facilitates low-pH-induced membrane fusion in endosomes to release viral genome. HA determines host tropism through receptor-binding site (RBS) variations, with H1 subtypes preferring α2,6-linked sialic acids in humans, as seen in 1918 and 2009 pandemics driven by mutations like E190D and G225D. As a major surface antigen, HA eliciting neutralizing antibodies, primarily against the variable head, complicating vaccine design due to antigenic drift. Drugs and antibodies target HA indirectly via NA inhibitors maintaining HA-NA balance or directly via stem-focused broadly neutralizing antibodies to block fusion. Therapeutic challenges include viral evolution evading immunity and potential for interspecies transmission.

Other names

Influenza A hemagglutinin H1HA1Influenza hemagglutinin subtype H1

Inhibition of receptor binding (antibodies blocking RBS); Prevention of membrane fusion (stem-targeted antibodies or fusion inhibitors); Neutralization of viral entry (anti-HA antibodies); Restoration of HA-NA functional balance (NA inhibitors reducing HA affinity mutations)