Haemagglutinin structure

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

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. 

The influenza virus is an RNA-(—)- virus and possesses its own RNA polymerase enzyme. The complete RNA genome codes for eight proteins - two structural (matrix) proteins M, and M2, haemagglutinin, and neuraminidase and four proteins involved in replication, three of which make up the polymerase enzyme. Substrates for this are the usual ribonucleosides and there has been some success with the use of nucleoside analogues as inhibitors of the enzyme. The drug ribavirin has been the most successful, although this has to be administered by aerosol. These days, its major use is for the treatment of infections caused by respiratory syncytial viruses (especially in children), since these can cause long-term morbidity. 

The spikes are of two types. One type (haemagglutinin) has a vital role in the first stages of infection, the penetration of host cells. The second type of spike is made of an enzyme called sialidase, whose role is to help newly formed viruses escape from the host cell so that they can move on to infect other cells. As part of this process, sialidase cleaves off sialic acid from oligosaccharides (short chains of carbohydrate units). These sialidase spikes have clefts that contain an acti ve site, into which bound sialic acid (Structure 3.1) fits during the cleavage process. This active site... 

The virion (the complete infective virus, such as exists extracellularly) consists of a core of either DNA or RNA (but not both) surrounded by a protective capsid (= shell) of one, or sometimes two, proteins. These two components are arranged in a highly ordered fashion that is characteristic of the particular kind of virus. Most of the viruses that infect animals are icosahedral (20-sided) and hence roughly spherical. But the viruses of measles and influenza are spirals. In the latter virus two kinds of protein (neuraminidase and haemagglutinin) form the capsid which is embedded in lipid, and this lipoprotein envelope encloses a coiled ribonucleoprotein tube. Poxviruses (which include the herpesviruses) are the largest known, brick-shaped and of very complicated structure. Many types of virus have a protein core around which the nucleic acid is arranged. 

Structure of the haemagglutinin-esterase-fiision glycoprotein of influenza C virus. 

Paulson, J.C., Skehel, J.J., and Wiley, D.C. (1988) Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature, 333,... 

Wilson LA., Skehel J.J., and Wiley D.C. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3A resolution. Nature 289 366-373. 

Rosenthal PB, Zhang X, Formanowski F, Fitz W, Wong CH, Meier-Ewert H, Skehel JJ, Wiley DC (1998) Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C... 

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. 

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