Hemagglutinins

Haemagglutinins are of great importance as surface antigens for some viruses, such as:

• the influenza haemagglutinin (Sautto GA et al. 2019)
• the measles haemagglutinin
• the rubella hemagglutinin

Hemagglutinins are the receptor-binding and membrane fusion glycoproteins of these viruses. The spike-like structures on the surface of influenza viruses are essentially formed from the two glycoproteins hemagglutinin (H, rod-shaped) and neuraminidase (N, mushroom-shaped). Haemagglutinin is responsible for binding the virus to the host cell and enables fusion with the cell membrane and penetration of the virus genome into the cytoplasm (Gamblin SJ et al. 2021). The neuraminidase causes the detachment of newly formed virus particles from the host cell. It also frees the virus from mucopolysaccharides and other structures in the upper respiratory tract, thus enabling the infection of further host cells.

The antigenic properties of both glycoproteins vary during a pandemic, and their activities may also vary in terms of recognition specificity and specific activity. The attachment of the virus to the surface of a cell is a polyvalent interaction between hemagglutinins on the virus and multiple copies of sialic acid, the terminal sugar of many carbohydrate side chains. Numerous studies (Gamblin SJ et al. 2021) have shown that the binding of sialic acid to receptors is species-specific:

If a patient's serum can prevent hemagglutination by a virus, this is an indication that the patient has produced specific antibodies when infected with such a virus. This phenomenon is detected with the hemagglutination inhibition test. In this test, the hemagglutinin titer (HHT titer) is used to determine the value of the highest serum dilution at which hemagglutination is still prevented.

Neuraminidase is the target for neuraminidase inhibitors, an important group of antiviral drugs.

1. De A (2018) Molecular evolution of hemagglutinin gene of influenza A virus. Front Biosci (Schol Ed). 10:101-118.
2. Gamblin SJ et al. (2021) Hemagglutinin Structure and Activities. Cold Spring Harb Perspect Med 11:a038638.
3. Garjani A et al. (2023) Forecasting influenza hemagglutinin mutations through the lens of anomaly detection. Sci Rep 13:14944.
4. Sautto GA et al. (2019) Hemagglutinin consensus-based prophylactic approaches to overcome influenza virus diversity. Vet Ital 55:195-201.