Influenza A virus hemagglutinin

Some early gIycodendrimers intended to make good inhibitors of influenza A virus hemagglutinin [49] were constructed following the divergent approach on a peptide core by solid phase methodology. Due to the lower symmetry of the core, the overall shape of these macromolecules was not as globular as claimed for Tomalia s Starburst dendrimers [51]. 

Mir-Shekari SY, Ashford DA, Harvey DJ, Dwek RA, Schulze IT. (1997) The glycosylation of the influenza A virus hemagglutinin by mammalian cells. J. Biol Chem. 272, 4027-4036. 

Suzuki, Y., Nagao, Y., Kato, H., Matsumoto, M., Nerome, K., Nakajima, K., and Nobusawa, E., 1986, Human influenza A virus hemagglutinin distinguishes sialyloligosaccharides in membrane-associated gangliosides as its receptor which mediates the adsorption and fusion processes of virus infection, J. Biol. Chem. 261 17057-17061. 

A special example of cell-cell interaction is the adherence of group B streptococci to canine, epithelial cells that are infected with influenza A virus. However, this capacity was blocked in the presence of tunicamycin, and this result supports the concept that adherence of streptococci to mammalian cells involves recognition of viral hemagglutinin, or its carbohydrate complement, the synthesis of which is blocked by tunicamycin.556... 

Fio. 1. (a) A view of the influenza virus hemagglutinin trimer showing jV-acetylneuraminic acid (3, in CPK form) bound, (b) The tetrameric unit of influenza A virus sialidase. The figures were generated using the PyMOL Molecular Graphics System (Delano, W.L. (2002) at http // www.pymol.org). 

The most striking feature of influenzavirus is the layer of spikes projecting outward from the surface (Fig. I). These spikes are the hemagglutinin (FIA) proteins of which there are estimated to be a few hundred copies per virion (Ruigrok et al, 1984 Amano and Hosaka, 1992). The HA spikes carry out both receptor binding and membrane fusion during infection. ELA of influenza A virus was the first enveloped virus surface protein to be studied by X-ray crystallography (Wilson et al, 1981),... 

Acetylation of mucin-bound and membrane-bound sialic acids makes them more resistant towards sialidase action [8,33,245,853,854]. This may be one of the reasons why intestinal mucins, especially of the colon, are often O-acetylated (ref. [245], and section 8.4.2). The high level of 0-acetylation of sialic acids observed in the endothelia of blood vessels, e.g, in liver, detected by histochemical methods using influenza C virus hemagglutinin, is assumed to have a similar function [234,235,730]. 

MECHANISMS OF ACTION AND RESISTANCE Amantadine and rimantadine inhibit an early step in viral replication, probably viral uncoating for some strains, they also have an effect on a late step in viral assembly probably mediated through altering hemagglutinin processing. The primary locus of action is the influenza A virus M2 protein, an integral membrane protein that functions as an ion channel. 

The orthomyxoviruses are enveloped viruses with a single-stranded, segmented RNA genome of negative polarity [11, 12]. There are five genera in the family Influenza virus A, B, and C, Thogotovirus, and Isavirus. Influenza A viruses are further divided into subtypes characterized by 16 different hemagglutinins... 

Influenza A viruses are important human and animal pathogens. Their primary natural hosts are aquatic birds from which they are occasionally transmitted to other species. In man they cause outbreaks of respiratory disease that occur as annual epidemics and less frequent pandemics. Influenza B viruses are also believed to be descendants of avian influenza A viruses, but are now largely restricted to humans where they cause respiratory infections as well. Influenza A and B viruses have two envelope glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA), both of which interact with sialic acid. 

Fig. 1 Sialic acid binding sites of the hemagglutinin (a) and the neuraminidase (b) of influenza A virus and the hemagglutinin-esterase-fusion protein of influenza C virus (c). Molecular surfaces of HA and HEF trimers and the NA tetramer are shown. Receptor-binding sites of HA, HEF and the hemadsorption site of NA are colored ye/tow. The catalytic sites of NA and HEF are colored green. Sialic acid moieties in the binding sites of HA and NA are shown as stick models. The figtffe is based on crystal structures IMQM, 1W20, and IFLC from Protein Data Bank...

Mitnaul LJ, Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV, Kobasa D, Kawaoka Y (2000) Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J Virol 74 6015-6020... 

Eisen MB, Sabesan S, Skehel JJ, Wiley DC. (1997) Binding of the Influenza A virus to cell-surface receptors structures of five hemagglutinin-sialyloligosaccharide complexes determined by X-ray crystallography. Virology HI, 19-31. 

Nobusawa, E., Aoyama, T., Kato, H., Suzuki, Y, Tateno, Y, and Nakajima, K., 1991, Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses. Virology 182 475-485. 

Figure 5.19 Schematic picture of a single subunit of influenza virus hemagglutinin. The two polypeptide chains HAj and HA2 are held together by disulfide bridges.

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