Target intelligence / Profile preview

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

Target
HA (H3)
Molecular classification
Viral surface glycoprotein, Class I fusion protein, Lectin, Receptor
01

Overview

Influenza A virus hemagglutinin (H3 subtype) is a critical surface glycoprotein responsible for the initial stages of viral infection and is a primary component of seasonal influenza vaccines [UniProt: P03437]. It functions as a lectin that binds to alpha-2,6-linked sialic acid receptors on human respiratory epithelial cells, followed by a conformational change in the acidic environment of the endosome that triggers membrane fusion [PubMed: 29133415]. As the primary antigen in seasonal influenza vaccines, H3 is subject to intense selective pressure, leading to frequent antigenic drift that allows the virus to evade pre-existing immunity [CDC: Influenza Antigenic Characterization]. This necessitates the annual monitoring and updating of the H3 component in trivalent and quadrivalent vaccines by global health organizations to ensure a match with circulating H3N2 strains [WHO: Influenza Vaccine Recommendations]. Beyond vaccines, hemagglutinin is a target for neutralizing monoclonal antibodies and fusion inhibitors like umifenovir, which aim to prevent viral entry and spread [PubChem: Umifenovir].

Other names
H3 hemagglutininHemagglutinin H3HA3Influenza A H3N2 hemagglutininHemagglutinin surface glycoprotein
02

Mechanism of action

Vaccines containing the H3 subtype induce the production of neutralizing antibodies that primarily target the globular head of the hemagglutinin protein, thereby blocking the virus from binding to host sialic acid receptors [CDC: How Influenza Vaccines Work]. Small molecule inhibitors such as umifenovir (Arbidol) act by binding to a hydrophobic pocket in the HA stem region, stabilizing the prefusion conformation and preventing the pH-induced structural rearrangement necessary for viral-endosomal membrane fusion [PubMed: 30674659].

03

Biological functions

Viral attachmentMembrane fusionReceptor bindingImmune response inductionEndocytosis mediation
04

Disease associations

InfectionInfluenza ASeasonal influenzaRespiratory tract infection
05

Safety considerations

Antigenic drift leading to vaccine mismatchEgg-adaptive mutations during vaccine manufacturing (e.g., loss of glycosylation sites)Hypersensitivity to vaccine components (e.g., egg protein)Risk of Guillain-Barre syndrome (rare)Original antigenic sin (blunted response to new strains)
06

Interacting drugs

Umifenovir

7 more in the full profile.

07

Biomarkers

Hemagglutination inhibition (HAI) titerMicroneutralization (MN) titerH3-specific IgG antibody levelsSingle radial hemolysis (SRH) area

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