Influenza A virus H3 hemagglutinin (H3 HA)

Influenza A virus H3 hemagglutinin is a major surface glycoprotein of the H3 subtype of Influenza A viruses, most notably the H3N2 strains responsible for significant seasonal morbidity. It functions as a class I viral fusion protein, mediating the initial attachment of the virus to sialic acid receptors on host respiratory cells and subsequently driving the fusion of the viral and endosomal membranes. As the primary target of the host's neutralizing antibody response, it is the central component of most influenza vaccines. However, the high rate of mutations in the HA head domain, known as antigenic drift, frequently leads to vaccine mismatch and necessitates annual updates to vaccine compositions. Beyond vaccines, H3 hemagglutinin is a target for antiviral development, including small-molecule inhibitors like umifenovir and broadly neutralizing monoclonal antibodies. These therapeutics typically work by blocking the receptor-binding site or preventing the conformational changes required for membrane fusion. The protein's structure consists of a globular head containing the receptor-binding site and a conserved stalk region that facilitates fusion. Monitoring efficacy against this target often involves hemagglutination inhibition assays to measure the strength of the antibody response. Challenges in targeting H3 HA include its high plasticity and the potential for egg-adapted mutations during the manufacturing of traditional vaccines.

Other names

H3HAHemagglutininH3N2 hemagglutininInfluenza A virus hemagglutinin H3

Inhibition of viral attachment to host cell sialic acid receptors and prevention of low-pH induced conformational changes required for membrane fusion.