Hemagglutinin (influenza)

Hemagglutinin (influenza)

Hemagglutinin (HA) is a glycoprotein found on the surface of the influenza virus. It is responsible for binding the virus to the cell that is being infected. Hemagglutinin is a major antigen against which protective antibodies are directed.

Structure

Hemagglutinin is a trimeric protein, meaning it is composed of three identical subunits. Each subunit consists of two polypeptides, HA1 and HA2, which are derived from a single precursor protein, HA0. The HA1 subunit is responsible for binding to the host cell's sialic acid receptors, while the HA2 subunit facilitates the fusion of the viral and cellular membranes, allowing the viral genome to enter the host cell.

Function

The primary function of hemagglutinin is to mediate the entry of the influenza virus into host cells. This process begins with the binding of HA1 to sialic acid residues on the surface of the host cell. This binding triggers endocytosis, a process by which the host cell engulfs the virus in a vesicle. Once inside the host cell, the acidic environment of the endosome induces a conformational change in HA, exposing the fusion peptide of HA2. This peptide inserts into the endosomal membrane, leading to the fusion of the viral and endosomal membranes and the release of the viral RNA into the host cell's cytoplasm.

Antigenic Variation

Hemagglutinin is subject to frequent genetic changes, which can lead to antigenic drift and antigenic shift. Antigenic drift refers to the gradual accumulation of mutations in the HA gene, resulting in minor changes to the protein's structure. These changes can allow the virus to evade the host's immune system, necessitating the annual update of the influenza vaccine.

Antigenic shift, on the other hand, involves the reassortment of HA genes between different influenza viruses, leading to the emergence of a novel HA subtype. This can result in pandemics, as the human population may have little to no pre-existing immunity to the new subtype.

Subtypes

There are 18 known subtypes of hemagglutinin, designated H1 through H18. These subtypes are used, along with the neuraminidase (NA) subtypes, to classify influenza viruses. For example, the H1N1 and H3N2 subtypes are commonly associated with seasonal influenza in humans.

Role in Vaccine Development

Hemagglutinin is a key target for influenza vaccines. The inactivated influenza vaccine and the live attenuated influenza vaccine both aim to elicit an immune response against HA, providing protection against infection. Due to the antigenic variability of HA, vaccines must be updated regularly to match the circulating strains.

Research and Therapeutics

Ongoing research is focused on developing universal influenza vaccines that target conserved regions of hemagglutinin, potentially providing broader and longer-lasting protection. Additionally, antiviral drugs that inhibit HA function are being explored as potential treatments for influenza.

See Also

• Influenza
• Neuraminidase
• Antigenic drift
• Antigenic shift
• Influenza vaccine