Influenza and Gangliosides
	Influenza is a viral disease caused by influenza viruses, and is the paradigm of a viral disease in which continued evolution of the virus is of paramount importance for animal epidemics and occasional pandemics of the disease in humans. Influenza viruses are differentiated into three types, A, B, and C, all of which recognize sialic acid and its derivatives as their functional receptors. Influenza A viruses are the most virulent of the three, and can be isolated from many kinds of animals, including humans, birds, pigs and horses as well as whales and sea lions. Influenza viruses have two kinds of spike glycoproteins in their envelope membranes (Fig.). One of them is hemagglutinin, which is essential for binding to cellular receptors such as gangliosides and sialylglycoproteins. The other is sialidase (neuraminidase), which is a receptor-destroying enzyme that cleaves the sialic acid from the viral receptor sugar chains. We confirmed the relation between molecular evolution of hemagglutinin and the functional structure of receptor sialyl sugar chains using gangliosides (1-4) and also the specificity of the viral sialidase to gangliosides (5,6). We confirmed that 1) the common receptor sialyl sugar chains for the human influenaza A and B viruses are Neu5Ac alpha2-6(or Neu5Ac alpha2-3 Gal beta1-4(3)GlcNAc beta1- (Sialyllacto-series type I and II sugar chains)(1,2), and 2)the host range selection of the receptor binding specificity of the influenza A virus hemagglutinin occurs during maintenance of the virus in different host cells which express different receptor sialo-sugar chains. This host range selection may be processed by host cell receptor level (3) and also by antibody pressure (4), because the change in receptor binding specificity ( 2-6 2-3 ) appears as a substitution of the amino acid (Leu226 Gln) located in the receptor binding pocket of the viral hemagglutinin (3), and the other change in receptor binding specificity ( 2-3 2-6 ) also occurs by the single amino acid substitution, Ser205 Tyr located in the antigenic site D outside the pocket (4). We also confirmed that 3) the derivatives of sugar chains, described above show neutralizing activity of the virus infection. Human influenza virus sialidase hydrolyzed the terminal sialic acid sequence of many kinds of gangliosides, but not the sialyl linkage on the inner galactose of GM1a (5). Human influenza virus sialidase hydrolyzed Neu5Ac2-3Gal linkage more preferentially than 2-6 linkage, indicating that the evolution of the sialidase molecule may be independent from that of hemagglutinin (6).
	Yasuo Suzuki (Department of Biochemistry, University of Shizuoka School of Pharmaceutical Sciences)
	References (1) Suzuki, Y et al. : Structural determination of gangliosides that binds to influenza A, B, and C viruses by an improved binding assay: strain-specific receptor epitopes in sialo-sugar chains. Virology, 189, 121-131, 1992 (2) Suzuki, Y : Gangliosides as influenza virus receptors. Variation of influenza viruses and their recognition of the receptor sialo-sugar chains. Prog. Lipid Res. (Review), 33, 429-457, 1994 (3) Ito, T et al. : Differentiation in sialic acid-galactose linkages in the chicken egg amnion and allantois. Influence Human influenza virus receptor specificity and variant selection. J. Virol. 71, 3357-3362, 1997 (4) Suzuki, Y et al. : Single amino acid substitution in an antigenic site of influenza virus hemagglutinin can alter the specificity of binding to cell associated gangliosides. J. Virol. 63, 4298-4302, 1989 (5) Sato, K et al. Specificity of the N1 and N2 sialidase subtypes of human influenza A virus for natural and synthetic gangliosides. Glycobiol. 8, 527-532, 1998 (6) Suzuki, Y et al.: Variation in sialyl sugar chain mediated recognition by the hemagglutinin and sialidase of human influenza viruses. Options for the control of influenza III., ed. by Brown, LE, Hampson, AW Webster, RG, pp.443-446, 1996, Elsevier Science BV
Sep.15, 1998