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Hemagglutinin
 

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Hemagglutinin




Hemagglutinin (HA) or '''haemagglutinin''' ( BE ) is an Antigen ic Glycoprotein found on the surface of the Influenza Virus es and is responsible for binding the virus to the Cell that is being infected. The name ''hemagglutinin'' comes from the Protein 's ability to cause Erythrocyte s to clump together (Nelson 2005).


SUBTYPES

There are at least 16 different HA antigens. These subtypes are labeled H1 through H16. The last, H16, was discovered only recently on influenza A viruses isolated from black-headed Gull s from Sweden and Norway (Fouchier 2005 ). The first three hemagglutinins, H1, H2, and H3, are found in Human influenza viruses.

A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. It has been reported that single Amino Acid changes in this avian virus strain's type H5 hemagglutinin have been found in human patients that "can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses" (Gambaryan 2005 , Suzuki 2005 ). This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by Proteolysis (Senne 1996 , Hatta 2001 ).


FUNCTIONS AND MECHANISMS OF ACTION

HA has two primary functions:
#the recognition of target Vertebrate cells, accomplished through the binding of these cells' Sialic Acid -containing Receptor s, and
#the fusion of host and viral endosomal membranes (White 1997 ), accomplished through the recruitment of HA Molecule s to the fusion site where some undergo conformational alterations to destabilize the Lipid Bilayer , thence cooperatively forming a fusion intermediate which associates the two bilayers.


STRUCTURE

HA is a homotrimeric integral membrane Glycoprotein . It is shaped like a Cylinder , and is approximately 135 Å ( Angstroms ) long. The three identical Monomer s that constitute HA are constructed into a central α Helix coil; three spherical heads contain the Sialic Acid binding sites. HA monomers are synthesized as Precursor s that are then Glycosylated and cleaved into two smaller Polypeptides : the HA1 and HA2 subunits. Each HA monomer consists of a long, helical chain anchored in the membrane by HA2 and topped by a large HA1 globule.


REFERENCES

  • Fouchier RAM, Munster V, Wallensten A, et al, 2005. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. ''J Virol'' vol 79, issue 5, pp2814-22.




  • Nelson DL and Cox MM, 2005. ''Lehninger's Principles of Biochemistry'', 4th edition, WH Freeman, New York, NY.




  • Weis WI, Brünger AT, Skehel JJ, et al, 1990. Refinement of the influenza virus hemagglutinin by simulated annealing. ''J Mol Biol'' vol 212, pp737-761.


  • White JM, Hoffman LR, Arevalo JH, et al, 1997. Attachment and entry of influenza virus into host cells. Pivotal roles of hemagglutinin. In ''Structural Biology of Viruses''. Chiu W, Burnett RM, and Garcea RL, editors. Oxford University Press, NY. pp80-104.



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