Glycoconjugate glycans as viral receptors

Abstract

The carbohydrate parts of cell surface glycoproteins, glycolipids, and proteoglycans constitute receptors for many enveloped as well as non-enveloped human viruses. The majority of viral receptors of carbohydrate nature are negatively charged, including sulfated glycosaminoglycans (GAGs) or glycans containing sialic acid. Not uncommonly, virus-carbohydrate interactions are responsible for specific tissue tropism, where the affinity of influenza virus for glycans in the respiratory tract containing (a2-6)-linked sialic acid is an important example. Similarly, the number and spacing of sulfates may guide viruses to optimal GAG molecules, although this remains unproven on tissue level. A further understanding of structure and tissue distribution of carbohydrate virus receptors and their viral ligands is essential for elucidating the pathogenesis of such viruses. Also neutral glycans such as histo-blood group substances may function as virus receptors. Here, natural resistance to a given viral disease may occur in a human subpopulation due to lack of such receptors caused by deletion-mutants in critical human genes. As regards antiviral applications, the receptor-destroying enzymes, in contrast to receptor binding proteins, at the surface of, for example, influenza virus have proven to be an excellent target for intervention, which is why sialic acid analogues are now in clinical use both for prophylaxis and treatment.