Haemagglutinin

Subunit vaccines based on the surface proteins of vims are also being explored. It has been demonstrated that the two major protective antigens are haemagglutinin (HA) and neuraminidase (NA). The genes for these antigens have been cloned and expressed in baculovims in insect cell culture (84). 

Watowich, S.I., et al. Crystal structures of influenza virus haemagglutinin in complex with high affinity receptor analogs. Structure 2 719-731, 1994. 

Fig. 1 A view of the influenza virus haemagglutinin (HA) monomer with the receptor fragment a-2,3-sialyUactose [a-Neu5Ac-(2,3)- 3-Gal-(1,4)-P-Glc] bound...

Specific proteins on the surface of virus particles, e.g. the haemagglutinins of influenza viruses (Fig. 3.8), mediate their adherence to glycoprotein receptors in the plasma membrane of host cells. Viruses make use of a variety of membrane glycoproteins as... 

All enveloped human vimses acquire their phospholipid coating by budding through cellular membranes. The maturation and release of enveloped influenza particles is illustrated in Fig. 3.8. The capsid protein subunits are transported flom the ribosomes to the nucleus, where they combine with new viral RNA molecules and are assembled into the helical capsids. The haemagglutinin and neuraminidase proteins that project fiom the envelope of the normal particles migrate to the cytoplasmic membrane where they displace the normal cell membrane proteins. The assembled nucleocapsids finally pass out from the nucleus, and as they impinge on the altered cytoplasmic membrane they cause it to bulge and bud off completed enveloped particles flxm the cell. Vims particles are released in this way over a period of hours before the cell eventually dies. 

Influenza (split virion)t Allantoic fluid from embryonated hens eggs infected with influenza viruses A and B 1 Harvest of viruses 2 Disruption with surface active agent 3 Blending of components of different serotypes Assay of haemagglutinin content by immunodiffusion Inoculation of embryonated hens eggs to exclude live virus... 

H2O2 The chemical symbol for hydrogen peroxide Hag Haemagglutinin Hag-1, Hag-2 Cleaved haemagglutinin subunits-1, -2 H E Haematoxylin and eosin hIL Human interleukin Hb Haemoglobin... 

Several carbohydrate-binding proteins have been isolated from Sambucus nigra and two haemagglutinins have been isolated from its bark. Its seeds contain a lectin that is related to the immunological properties of the bark. One of its carbohydrate-binding proteins, called nigrin, is made of two subunits and is reported to cause red blood cells to clump. 5... 

R. Roy, D. Zanini, S. J. Meunier, and A. Romanowska, Solid phase synthesis of dendritic sialoside inhibitors of influenza A virus haemagglutinin, J. Chem. Soc. Chem. Commun. (1993) 1869-1872. 

Wiley, D.C., Skehel, J.J., and Waterfield, M. (1977) Evidence from studies with a cross-linking reagent that the haemagglutinin of influenza virus is a trimer. Virology 79, 446-448. 

Kajava, A. V., Cheng, N., Cleaver, R., Kessel, M., Simon, M. N., Willery, E., Jacob-Dubuisson, F., Locht, C., and Steven, A. C. (2001). Beta-helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins. Mol. Microbiol. 42, 279-292. 

Wharton SA, Martin SR, Ruigrok RW, et al. Membrane fusion by peptide analogues of influenza virus haemagglutinin. J Gen Virol 1988 69(Pt 8) 1847-1857. 

Similar synthetic vaccines have also been constructed which confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. While coupling to a carrier is generally required to elicit an immunological response, some carriers are inappropriate due to their ability to elicit a hypersensitive reaction, particularly when repeat injections are undertaken. Such difficulties can be avoided by judicious choice of carrier. Often a carrier normally used for vaccination is itself used, e.g. tetanus toxoid has been used as a carrier for peptides derived from influenza haemagglutinin and Plasmodium falciparum. 

The influenza neuraminidase is one of two major glycoproteins located on the influenza virus membrane envelope (the other one is haemagglutinin, HA). As the name suggests. 

Robinson, H.L., L.A. Hunt, and R.G. Webster, Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine, 1993.11(9) 957-60. 

Both GW, Sleigh MJ, Cox NJ, Kendal AP. Antigenic drift in influenza virus H3 haemagglutinin from 1968 to 1980 multiple evolutionary pathways and sequential amino acid changes at key antigenic sites. J Virol 1983 48 52-60. 

Rogers GN, Paulson JC. Receptor determinants of human and animal influenza virus isolates difference in receptor specificity of the H3 haemagglutinin based on species of origin. Viroloy 1983 127 361-373. 

Burnett FM. Mucins and mucoids in relation to influenza virus action. IV. Inhibition by purified mucoid of infection and haemagglutinin with the virus strain WSE. Aust J Exp Biol Med Sci 1947 26 381-387. 

Botulinum toxin A complexed with haemagglutinin is currently employed medicinally to counter involuntary facial muscle spasms, e.g. around the eye. Very small (nanogram) amounts are injected locally and result in the destruction of the acetylcholine release mechanism at the neuromuscular junction. Since new nerve junctions will gradually be formed over two months or so, the result is not permanent, and the treatment will need to be repeated. It has also been found useful in easing muscle spasticity in children with cerebral palsy. 

R. Wagner, M. Matrosovich, and H.-D. Klenk, Functional balance between haemagglutinin and neuraminidase in influenza virus infections, Rev. Med. Virol, 12 (2002) 159-166. 

Roy and coworkers 70 71] described the solid state preparation of the first four generations (e.g., 38) of the dendritic sialoside inhibitors of influenza A virus haemagglutinin... 

Scheme 4.13. Dendritic sialoside inhibitors of influenza A virus haemagglutinin constructed via the solid phase synthesis of a lysine-based superstructure.

HAU HECS Hep cells HPRT HSV HTC cells IAA ITES haemagglutinin unit human endothelial cell supernatant human epithelial cells hypoxanthine phosphoribosyl transferase herpes simplex virus hepatoma tissue culture cells indole acetic acid medium supplement containing insulin, transferrin, ethanolamine and selenium... 

Jabbal-Gill, I., Fisher, A. N., Rappuoli, R., Davis, S. S., and Ilium, L. (1998), Stimulation of mucosal and systemic antibody responses against Bordetella pertussis filamentous haemagglutinin and recombinant pertussis toxin after nasal administration with chitosan in mice, Vaccine, 16,2039-2046. 

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