Hemagglutinin

Illustration showing influenza virus attaching to cell membrane via the surface protein hemagglutinin

Hemagglutinins (alternatively spelt haemagglutinin, from the Greek haima, 'blood' + Latin gluten, 'glue') are homotrimeric glycoproteins present on the protein capsids of viruses in the Paramyxoviridae and Orthomyxoviridae families.[1][2][3] Hemagglutinins are responsible for binding to receptors, sialic acid residues, on host cell membranes to initiate virus docking and infection.[4][5]

Specifically, they recognize cell-surface glycoconjugates containing sialic acid on the surface of host red blood cells with a low affinity and use them to enter the endosome of host cells.[6] In the endosome, hemagglutinins undergo conformational changes due to a pH drop to of 5–6.5 enabling viral attachment through a fusion peptide.[7]

Virologist George K. Hirst discovered agglutination and hemagglutinins in 1941.[8] Alfred Gottschalk proved in 1957 that hemagglutinins bind a virus to a host cell by attaching to sialic acids on carbohydrate side chains of cell-membrane glycoproteins and glycolipids.[9]

The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro.[10]

  1. ^ Couch, Robert B. (1996), Baron, Samuel (ed.), "Orthomyxoviruses", Medical Microbiology (4th ed.), Galveston (TX): University of Texas Medical Branch at Galveston, ISBN 978-0-9631172-1-2, PMID 21413353, retrieved 30 January 2024
  2. ^ "Paramyxoviridae - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 30 January 2024.
  3. ^ Skehel, John J.; Wiley, Don C. (June 2000). "Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin". Annual Review of Biochemistry. 69 (1): 531–569. doi:10.1146/annurev.biochem.69.1.531. ISSN 0066-4154. PMID 10966468.
  4. ^ Nobusawa, E. (October 1997). "[Structure and function of the hemagglutinin of influenza viruses]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 55 (10): 2562–2569. ISSN 0047-1852. PMID 9360372.
  5. ^ Luo, Ming (8 November 2011), Influenza Virus Entry, Advances in Experimental Medicine and Biology, vol. 726, Boston, MA: Springer US, pp. 201–221, doi:10.1007/978-1-4614-0980-9_9, ISBN 978-1-4614-0979-3, retrieved 17 November 2024
  6. ^ Bangaru, Sandhya; Lang, Shanshan; Schotsaert, Michael; Vanderven, Hillary A.; Zhu, Xueyong; Kose, Nurgun; Bombardi, Robin; Finn, Jessica A.; Kent, Stephen J.; Gilchuk, Pavlo; Gilchuk, Iuliia (2019). "A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface". Cell. 177 (5): 1136–1152.e18. doi:10.1016/j.cell.2019.04.011. PMC 6629437. PMID 31100268.
  7. ^ Medeiros, R.; Escriou, N.; Naffakh, N.; Manuguerra, J. C.; van der Werf, S. (10 October 2001). "Hemagglutinin residues of recent human A(H3N2) influenza viruses that contribute to the inability to agglutinate chicken erythrocytes". Virology. 289 (1): 74–85. doi:10.1006/viro.2001.1121. ISSN 0042-6822. PMID 11601919.
  8. ^ Kolata, Gina (26 January 1994). "George Keble Hirst, 84, Is Dead; A Pioneer in Molecular Virology". The New York Times. ISSN 0362-4331. Retrieved 14 May 2024.
  9. ^ Henry, Ronnie; Murphy, Frederick A. (October 2018). "Etymologia: Hemagglutinin and Neuraminidase". Emerging Infectious Diseases. 24 (10): 1849. doi:10.3201/eid2410.ET2410. PMC 6154157.
  10. ^ Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York: WH Freeman.