Influenza A virus hemagglutinin (H3) (HA (H3))

The Influenza A virus hemagglutinin (H3) is a primary surface glycoprotein of the H3N2 subtype, essential for viral entry into host cells (UniProt: P03437). It functions as a trimeric protein that recognizes and binds to terminal alpha-2,6-linked sialic acids on host cell surface glycoproteins in the human respiratory tract, initiating receptor-mediated endocytosis (PubMed: 22301554). Following internalization, the acidic environment of the endosome triggers a massive conformational change in the HA molecule, leading to the fusion of the viral and endosomal membranes and the release of the viral genome into the cytoplasm (PubMed: 11061435). Due to its prominent position on the viral envelope, HA is the principal target for neutralizing antibodies and the primary component of seasonal influenza vaccines (CDC, 2023). However, the protein is subject to continuous antigenic drift, where mutations in the globular head domain allow the virus to escape pre-existing immunity, necessitating annual vaccine updates (PubMed: 29155429). Therapeutic interventions targeting HA include fusion inhibitors like umifenovir and various broadly neutralizing monoclonal antibodies currently in clinical development (PubMed: 30639431, PubMed: 27435445).

Other names

H3 hemagglutininHemagglutinin surface glycoproteinHA proteinH3N2 HAInfluenza A virus H3N2 hemagglutinin

Neutralization of viral infectivity by blocking the interaction between the hemagglutinin globular head and host sialic acid receptors, or by inhibiting the pH-dependent conformational rearrangement of the HA2 subunit required for membrane fusion (PMID: 30639431, PMID: 27435445).