Influenza haemagglutinin

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. 

Wiley DC, Wilson lA, Skehel JJ. (1981) Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvment in antigenic variation. Nature 289, 373-378. 

Rogers GN, Paulson JC, Daniels RS, Skehel JJ, Wilson lA, Wiley DC. (1983) Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature 304, 76-78. 

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... 

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. 

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. 

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. 

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.

Bizebard, T., Gigant, B., Rigolet, P., Rasmussen, B., Diat, O., Bosecke, P., Wharton, S. A., Skehel, J. J., and Knossow, M. (1995). Structure of influenza virus haemagglutinin complexed with a neutralizing antibody. Nature 376, 92-94. 

Influenza viruses are enveloped by an host cell-derived lipid membrane which is penetrated by numerous copies of three distinct types of virally coded molecules haemagglutinin (HA), neuraminidase (NA) and M protein. Fig. (2). 

---