The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.

A convenient synthetic route to a new type of artificial glycoconjugate polymer has been designed to develop biomedical materials using oligosaccharide moieties as recognition signals. An amino function was introduced to the reducing end of lactose and N,N‘-diacetylchitobiose with ammonium hydrogen carbonate and then was allowed to react with p-vinylbenzoyl chloride. The N-glycosidation proceeded stereospecifically in one flask to give only the β-glycoside without any protection and deprotection steps. The resulting p-vinylbenzamide glycoside derivatives were homo- and copolymerized with acrylamide using 2,2‘-azobisisobutyronitrile as initiator in dimethyl sulfoxide at 60 °C. The interaction of the glycopolymers with lectins was investigated by means of a two-dimensional immunodiffusion test in agar and inhibition of the hemagglutinating activity. The specificity of lectins with these glycopolymers was similar to that reported for naturally-occurring glycoconjugates. Binding between wheat germ agglutinin lectin (WGA) and poly((p-vinylbenzamido)-β-diacetylchitobiose) was increased by 103 times compared with that of the oligosaccharide itself. The enhancement was attributed to the presence of the hydrophobic phenyl aglycon as well as the high density, multiantennary disaccharide ligands along the polymer chain. The present synthetic method is useful to introduce biologically important, complex oligosaccharides into glycopolymers.

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Natural-abundance carbon-I 3 n.m.r. spectra of all the glucobioses and of four selected glucotrioses in aqueous solution have been measured and are discussed. Peak assignments were made on the basis of comparison with the spectra of methyl glucopyranosides, four mono-0-methylglucoses and five methyl glucobiosides. Carbon-I 3 n.m.r. spectroscopy proved to be a useful tool for stereochemical characterisation of these oligosaccharides. In addition, carbon-I 3 n.m.r. spectra of the a-limit dextrins from glycogen and amylopectin have been measured and the differences between them are discussed.SPECTROMETRIC methods (i.r.,l o.r.d.,2 and lH n.m.r.3~4) have been used for establishing the configuration of glycosidic linkages of oligosaccharides and polysaccharides. The Karplus equation in lH n.m.r. has been applied extensively in the structural studies of monosaccharide pyranose and furanose derivatives.5 Positions of linkage in oligosaccharides have been determined by chemical methods and by biochemical degradation.+lO Recently, the 13C n.m.r. spectra of monosaccharides 11,12 and some common oligosaccharides 13*14 have been published and interpreted. These reports show that 13C chemical shift differences in sugars could be explained in terms of steric hindrance and proximity effectsWe have already reported that 13C n.m.r. spectroscopy can be used for the determination of the anomeric configurations of glucobi~ses.~~ We now describe the application of 13C n.m.r. to the configurational and conformational analysis of glucose oligomers and polymers, as well as to the determination of their linkage positions. Some tentative assignments l5 arc corrected on the basis of further data reported here. RESULTS AND DISCUSSIONIn 13C n.m.r. spectroscopy, it is difficult and laborious t o give a full peak assignment of sugar carbon atoms, although information from previous work has made it considerably ~imp1er.ll-l~ Roberts and his co-workers l1 showed that (a) methylation of a hydroxy-group effects