Influenza-virus hemagglutin

F. Lanni, D. G. Sharp, E. A.Eckert, E. S.Dillon, D.Beard and J. W. Beard, The Egg White Inhibitor of Influenza Virus Hemagglutination. I. Preparation and Properties of Semipur ified Inhibitor, J. biol. Chem. 179, 1275-1287 (1949). 

Rosenberg, A., Howe, C., and Chargaff, E., 1956, Inhibition of influenza virus hemagglutination by a brain lipid fraction. Nature 177 234-235. 

M. Mammen, G. Dahmann, and G. M. Whitesides, Effective inhibitors of hemagglutination by Influenza Virus synthesized from polymers having active ester groups. Insight into mechanisms of inhibition, /. Med. Chem., 38 (1995) 4179-4190. 

L5. Laurell, A.-B., Inhibitor capacity of some purified human serum proteins on hemagglutination by influenza virus. Acta Pathol, et Microbiol. Scand. 49, 213 (1960). 

Fig. 1.4 Hemagglutination assay results from the active fraction of the red alga Gigartina skottsbergii. a Red blood cells (RBCs) hemagglutinate in the presence of influenza virus top row) and with extract A4 -t- virus or extract A4 alone. The bottom two rows present the back titration of the virus used in this experiment, b In contrast to the other anti-influenza drugs (ribavirin, amantadine, rimantadine, and zanamivir) that do not induce hemagglutination of human as well as chicken RBCs, extract A4 does it in a dose-dependent manner...

This cooperative effect of several ligands at the surface of a liposome was recently demonstrated by the inhibition of agglutination of erythrocytes (natural vesicles covered with sialic acids) with the influenza virus by means of sialyl gangliosides. The lowest concentration of sialyl derivatives required for the inhibition was found to be 10 pM in solution whereas it was 20 nM at the surface of a vesicle. Actually, arrays of sialic acid at the surface of liposomes were found to be moderately more effective than sialic acid groups linked to a soluble polymer but as good or better than the best known naturd inhibitors of hemagglutination (i.e. mucins and macroglobulins) [150]. 

The influenza virus is surrounded by a membrane containing, among other proteins, many molecules of the hemagglutination (HA) protein (named for its abil-... 

The existence of specific receptors for transferrin on the reticulocyte membrane was implied by the work of Jandl and associates, who observed that trypsin virtually abolished the ability of reticulocytes to take up iron from transferrin without affecting other metabolic functions of the cells (8). Whether the effect of the enzyme was to cleave the receptor from the cell membrane or to degrade it proteolytically was not clear. Neuraminidase treatment also depressed iron uptake by reticulocytes, but to a much lesser degree than trypsin and only at much higher concentrations than needed to abolish the hemagglutinating effects of influenza virus. Subsequent work from Morgan s laboratory has confirmed these results and has shown further that binding of transferrin to the receptor protects it from proteolytic enzymes (70). 

Hemagglutination by heat-treated, influenza virus is inhibited by a number of sialoproteins present in serum and animal secretions. ... 

Inhibitor of hemagglutination of human erythrocytes by influenza virus... 

Influenza vims strain A/HKx31 was propagated in embryonated chicken eggs. The influenza virus titer ranged from 1 x lo to 1 x lo EID50 as determined by hemagglutination assay with chicken red blood cells. Influenza... 

In a chicken embryo hemagglutination valence-reduction test, Yan et al. (2002) investigated the inhibition of influenza virus A3 by the Lamiaceae Mosla chinensis EO. The authors assessed the activity of the EO for treatment against pneumonia in experiments with mice and found that the cytopathic effect (CPE) caused by influenza virus A3 was reduced in Vero cells by this EO. The hemagglutination valence was reduced from 1 1280 to 1 20 and 1 160 at concentrations of 500, 250, and 50 mg/mL in 9-day-old chicken, respectively. At a dosage of 100 (ig/g/d, the therapeutic treatment of mice against pneumonia was successful. 

Morner isolated two water-soluble glycoproteins (called urinary mucoids) from urine by alcohol precipitation, redissolution, and precipitation with chloroform in the presence of acetic acid 4)- Interest in these substances was stimulated by the isolation of a purified urinary glycoprotein which proved to be a strong inhibitor of the hemagglutination by influenza virus and similar viruses 82, 83). Sialic acid (see below) is said to be removed from the glycoprotein by the virus. 

Sialic acid was the first virus receptor identified. Hirst and McClelland and Hare discovered that influenza virus is able to hemagglutinate and that adsorbed virus is eluted from erythrocytes on incubation at 37°C, indicating an enzymatic destruction of a receptor substance on the cells [1, 2]. When a similar enzymatic activity was subsequently detected in Vibrio cholerae cultures, the term receptor-destroying enzyme was introduced [3]. The substance released by the viral enzyme from soluble hemagglutination inhibitors was initially characterized as a carbohydrate of low molecular weight [4] and then identified in crystalline form as A-acetyl-o-neuraminic acid [5]. Thus, it was clear that the receptor determinant of influenza virus was sialic acid and that the viral enzyme was a neuraminidase. Furthermore, for the first time an important biological function of sialic acid had been identified. 

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