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Haemagglutinin glycoprotein is a trimeric, integral membrane protein that projects from the surface of the influenza virus as spikes roughly 135 Å long. Each HA monomer is initially synthesized as the precursor HA0, which is proteolytically cleaved into HA1 (receptor binding) and HA2 (membrane fusion and anchor domains). The globular HA1 domain contains the receptor binding site, which recognizes terminal sialic acid residues on host cell surface glycoproteins. The HA2 subunit contains a fusion peptide that, upon exposure to acidic pH in endosomes, undergoes structural rearrangement to mediate viral and host membrane fusion. HA is highly antigenically variable, underpinning both seasonal influenza epidemics and pandemic outbreaks, and is a primary component of influenza vaccine formulations. Targeting the haemagglutinin glycoprotein with neutralizing antibodies or entry inhibitors is a cornerstone of influenza antiviral strategies.
Neutralizing antibody binding to globular head domain blocks receptor attachment and/or triggers immune clearance. Fusion inhibitors prevent conformational change necessary for membrane fusion.
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