Hemagglutinin (HA) or Haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro. The process is like this: Hemagglutinin (HA) binds to the monosaccharide sialic acid which is present on the surface of its target host cells. The cell membrane then engulfs the virus through endocytosis and forms endosome. The cell then attempts to begin digesting the contents of the endosome by acidifying its interior and transforming it into a lysosome. When the pH within the endosome drops to 6.0, the HA molecule becomes partially unfold, and releasing a very hydrophobic portion of its peptide chain that was previously hidden within the protein. This so-called "fusion peptide" acts like a molecular grappling hook by inserting itself into the endosomal membrane and locking on. Then, when the rest of the HA molecule refolds into a new structure and pulls the endosomal membrane right up next to the virus particle's own membrane, causing the two to fuse together. Once this has happened, the viral RNA genome enters into the cell's cytoplasm.
The main function of the Neuraminidase (NA) might be to remove receptors for influenza virus from newly formed virus particles so allowing these to be released and spread the infection. Another function of flu virus neuraminidase might be to destroy sialic acid containing inhibitors for the virus in the mucous secretions of the respiratory tract, so enabling the virus to more easily infect cells, and there may be other functions as yet undiscovered.
Studies have revealed that the stem N-glycans of HA is crucial for virus replication. In both culture systems, growth of virus lacking this glycans was completely blocked at 37 °C and inhibited at 33 °C. It is concluded that the stem N-glycans is indispensable for the formation of replication-competent influenza viruses.
Antibody that binds to the cap region of the Hemagglutinin (HA) protein can possibly block the binding of the virus to the sialic acid, and hence could potentially prevent virus infection, or have neutralizing activity. Antibody raised from vaccination of hemagglutinin antigen can protect vaccinee from virus infection.