Receptor-Destroying Enzymes

Because of the NA receptor-destroying enzyme activity, the sites of viral proteins on the cell surface are devoid of terminal sialic acid residues. Desialation is necessary to prevent aggr ation of the progeny virions, which greatly decreases infectivity. 

In concurrent investigations with R. Brossmer, crystalline 3 -0-(N-acetylneuraminyl)lactose was isolated from cow colostrum and demonstrated to be a substrate for influenza virus enzyme and for the receptor-destroying enzyme of Vibrio cholerae. The structure of N-acetylneuraminic acid, then still a matter of contention, was clarified by chemical degradation, and the configuration at C-4 that had remained unknown was established. Finally, the acid was synthesized in good yield (with G. Baschang). 

Keywords Ganglioside Mucins Neuraminidase Receptor binding Receptor-destroying enzyme Sialate-O-acetylesterase 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. 

Burnet FM, Stone JD (1947) The receptor-destroying enzyme of V. cholerae. Aust J Exp Biol Med Sci 25 227-233... 

Herrler G, Rott R, Klenk HD, Muller HP, Shukla AK, Schauer R (1985) The receptor-destroying enzyme of influenza C virus is neuraminate-O-acetylesterase. EMBO J... 

Hofling K, Klenk HD, Herrler G (1997) Inactivation of inhibitors by the receptor-destroying enzyme of influenza C virus. J Gtm Virol 78 567-570... 

Kristiansen M, Froystad MK, Rishovd AL, Gjoen T (2002) Characterization of the receptor-destroying enzyme activity from infectious salmon anaemia vims. J Gen Virol 83 2693-2697... 

Vlasak R, Luytjes W, Leider J, Spaan W, Palese P (1988) The E3 protein of bovine coronavirus is a receptor-destroying enzyme with acetylesterase activity. J Virol 62 4686 690... 

Neuraminic acid-containing components of cellular membranes have acquired considerable interest recently, because they play a role in the attachment and penetration of virus particles. The virus receptors of the cellular membrane can be destroyed by an enzyme from V. cholerae (receptor destroying enzyme). This enzyme has proved to be very specific for neuraminic acid. 

Figure 4. Viral sialate-O-acetylesterases as Receptor-Destroying Enzymes . The chromatograms (HPLC, fluorescent Sia derivatives [35]) show the conversion of Neu4,5Ac2 and Neu5,9Ac2 into NeuSAc under the influence of mouse hepatitis and influenza C viruses, respectively.

The receptor for influenza C is assumed to be 9-0-acetyl sialic acid, based on the esterase activity of its receptor-destroying enzyme [10]. In vivo, 9-O-acetyl sialic acids are added selectively to glycoproteins and glycolipids in a limited range of cell types, although these cell types are reasonably widely distributed [11], including mucosal epithelia. A putative receptor protein, a 40 kDa mucin heavily modified by 9-O-acetyl sialic acid, is present on apical surfaces of permissive MDCK cells and is rapidly and constitutively endocytosed [12],... 

Herrler G, GroP HJ, Brossmer R. (1995) A synthetic sialic acid analogue that is resistant to the receptor-destroying enzyme can be used by the influenza C virus as a receptor determinant for infection of cells. Biochem. Biophyt. Res. Comm. 216, 821-827. 

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