Influenza Hemagglutinin (HA) Protein

Hemagglutinin (HA) protein is a key antigenic glycoprotein on the surface of influenza viruses. It plays a critical role in viral entry and is a target for flu vaccines. This guide delves into the structure, function, and subtypes of HA protein, providing an in-depth look at its significance in influenza biology.

Detailed Structure of Hemagglutinin (HA) Protein

The HA protein is a trimeric glycoprotein, meaning it is composed of three identical subunits. Each subunit has two major components:

  1. The Globular Head Domain:

    • Composed of chains A, C, and E.
    • This region is responsible for receptor binding and is the main target of neutralizing antibodies.
  2. The Stem Domain:

    • Composed of chains B, D, and F.
    • It anchors the protein to the viral membrane and plays a role in the fusion of the viral and host cell membranes.

The cylindrical shape of the HA trimer facilitates its function in binding and fusion. Advanced imaging techniques, like cryo-electron microscopy, have provided insights into its dynamic structural changes during viral entry.

Biological Function of HA Protein

The HA protein is crucial for influenza virus infection, performing two main functions:

1. Receptor Binding

  • The HA protein binds to sialic acid-containing receptors on the surface of host cells. This specificity determines the host range of the virus.

2. Membrane Fusion

  • After binding, HA undergoes a conformational change triggered by the acidic environment of the endosome, facilitating the fusion of the viral envelope with the host membrane.

Interestingly, the term "hemagglutinin" originates from its ability to cause erythrocyte agglutination in vitro, a property widely used in diagnostic assays.

Influenza HA Subtypes and Their Significance

The HA protein exists in 16 distinct subtypes (H1–H16), each paired with one of nine neuraminidase (NA) subtypes, giving rise to diverse influenza A strains.

Key Human-Associated Subtypes:

  • H1N1: Known for its role in seasonal influenza and the 2009 pandemic.
  • H3N2: A major cause of severe seasonal influenza, particularly in older adults.

Zoonotic and Emerging Subtypes:

  • H5N1: Associated with avian influenza, with occasional human infections.
  • H7N9: A subtype with pandemic potential, requiring close monitoring.

Together, these subtypes highlight the dynamic evolution and adaptation of influenza viruses, necessitating continual surveillance and vaccine updates.


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