Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin.

New technologies are urgently required for rapid surveillance of the current H5N1 avian influenza A outbreaks to gauge the potential for adaptation of the virus to the human population, a crucial step in the emergence of pandemic influenza virus strains. Owing to the species-specific nature of the interaction between the virus and host glycans, attention has recently focused on novel glycan array technologies that can rapidly assess virus receptor specificity and the potential emergence of human-adapted H5N1 viruses.

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Glycan Microarray Technologies: Tools to Survey Host Specificity of Influenza Viruses

Differential sensitivity of human, avian, and equine influenza A viruses to a glycoprotein inhibitor of infection: selection of receptor specific variants.

Glycosyltransferases and their use in assessing oligosaccharide structure and structure-function relationships.

Publisher Summary Viral infection is initiated by attachment of the virus to the host cell. Viral adsorption to cells is mediated by a viral attachment protein that binds to a specific cell surface receptor. The viral attachment protein has been identified for many animal viruses. It has been established that receptor recognition is specific and can influence the host range of a virus. Details of the virus–cell interaction at the molecular level are beginning to emerge for myxoviruses and paramyxoviruses. This is because of major advances in the elucidation of the structure of the viral hemagglutinin, especially for influenza virus, to improved methods for the analysis of receptor specificity and insights into the mechanisms of viral penetration of cellular membranes. The value of elucidating the details of virus–host recognition probably goes far beyond understanding the host–parasite relationship. The factors relevant to viral recognition, attachment, and penetration are similar to those of the ligand–receptor and cell–cell interactions of higher organisms. Thus, it is anticipated that in the future concepts evolving from the field of virus, receptors will merge with those from other types of receptor interactions represented in this treatise.

Interactions of Animal Viruses with Cell Surface Receptors

Inhibitors of hemagglutination by type A2 influenza virus and a recently isolated strain of type B influenza virus were separated by sucrose density gradient centrifugation and agarose gel filtration from horse serum. Using selected reagents, it was demonstrated that the active substituent on the horse serum inhibitor of A2 influenza virus was 4-O-acetyl-N-acetylneuraminic acid; however, the active substituent on the inhibitor of the influenza B virus was shown to be N-acetylneuraminic acid (NANA). Sodium metaperiodate treatment of a component of horse serum resulted in a 10 to 15-fold enhancement of inhibitory activity against the type B virus, whereas the A2 inhibitor was completely destroyed. Since this enhancement did not occur with influenza B viruses isolated prior to 1965, it was considered that this sensitivity to an oxidized NANA glycoside may have been a reflection of an antigenic change which occurred at that time. The use of different virus strains and selected chemical reagents to define the important sialic acid prosthetic groups active in inhibition was described.

Substituted Sialic Acid Prosthetic Groups as Determinants of Viral Hemagglutination

Influenza virus neuraminidase and the viral surface

The heterogeneity of human thyroglobulin.

Sera from fifty-six adults (males and females) were tested for free thyroglobulin and anti-thyroglobulin antibodies by electrophoretic immunoretention and chromatographic techniques using 131I-labelled thyroglobulin. The results were also compared with those previously reported in seventy-two parturient women and their newborn infants as well as three athyrotic cretins.

The results show that from one-half to two-thirds of normal non-pregnant females and from one-third to one-half of normal men have some material in their serum which binds labelled thyroglobulin and which may be anti-thyroglobulin antibody. A non-specific binding could not be excluded. The incidence of this phenomenon tends to have a positive correlation with age. On the other hand, one-fifth to one-third of newborn infants have `free thyroglobulin'-like substance in their serum (0.005–0.05 μg/ml). This was also found in a significantly smaller proportion in adults but was a particularly rare finding in non-pregnant women.

The implications of these findings on current immunological concepts are discussed.

G. Belyavin

Papers

Substituted Sialic Acid Prosthetic Groups as Determinants of Viral Hemagglutination

Influenza virus neuraminidase and the viral surface

The heterogeneity of human thyroglobulin.

Thyroglobulin and thyroglobulin antibodies in the serum of normal adults

Structure and composition of the n2 neuraminidase of influenza virus Effect of carbohydrate content on the validity of molecular weight estimations