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  • Review Article
  • Published:

The sweet spot: defining virus–sialic acid interactions

Nature Reviews Microbiology volume 12, pages 739–749 (2014)Cite this article

Subjects

Key Points

  • Many viruses engage sialylated glycans to bind to and infect cells. Sialic acid-binding viruses include influenza virus, reovirus, adenovirus and rotavirus, which bind to host receptors via their stalk-like attachment proteins.

  • Glycan microarray technology has enabled the rapid identification of specific carbohydrate ligands for several viruses. This technology has been used to discern glycan-binding preferences between closely related strains, including pathogenic influenza virus isolates.

  • Improvements in X-ray crystallography have enabled the virus–glycan interaction to be studied in detail and, coupled with reverse genetics approaches, structure–function relationships of virus–glycan interactions can be determined in vitro and in vivo.

  • The complexity of virus–sialic acid interactions is remarkable, as linkage basis and sialic acid modifications, such as sulphation, influence binding capacity. Preferences in glycan engagement influence influenza virus host range and modulate tissue tropism.

  • Virus–sialylated glycan interactions are an important therapeutic target, and structure–function analysis has facilitated drug development and may improve oncolytic vector design.

Abstract

Viral infections are initiated by attachment of the virus to host cell surface receptors, including sialic acid-containing glycans. It is now possible to rapidly identify specific glycan receptors using glycan array screening, to define atomic-level structures of virus–glycan complexes and to alter the glycan-binding site to determine the function of glycan engagement in viral disease. This Review highlights general principles of virus–glycan interactions and provides specific examples of sialic acid binding by viruses with stalk-like attachment proteins, including influenza virus, reovirus, adenovirus and rotavirus. Understanding virus–glycan interactions is essential to combating viral infections and designing improved viral vectors for therapeutic applications.

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Figure 1: Sialic acid types and glycosidic linkage.
Figure 2: Influenza virus binding to differentially linked sialic acids.
Figure 3: T1 and T3 reovirus σ1 proteins differentially bind to sialylated glycans.
Figure 4: Interaction between adenovirus 37 and glycan.
Figure 5: The VP8* domain of rotavirus VP4 differentially engages glycans.

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Acknowledgements

The authors' work was supported by US Public Health Service awards R01 AI76983 and R37 AI38296 and the Elizabeth B. Lamb Center for Pediatric Research.

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Author notes

  1. Kerstin Reiss

    Present address: Present address: Institute of Complex Systems (ICS.6), Forschungszentrum Julich, 52425 Julich, Germany.,

  2. Dirk M. Reiter

    Present address: Present address: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.,

  3. Jennifer E. Stencel-Baerenwald and Kerstin Reiss: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine,

    Jennifer E. Stencel-Baerenwald & Terence S. Dermody

  2. Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine,

    Jennifer E. Stencel-Baerenwald & Terence S. Dermody

  3. Interfaculty Institute of Biochemistry, University of Tubingen, Tubingen, 72076, Germany

    Kerstin Reiss, Dirk M. Reiter & Thilo Stehle

  4. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, 37232, Tennessee, USA

    Thilo Stehle & Terence S. Dermody

Authors
  1. Jennifer E. Stencel-Baerenwald
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Corresponding authors

Correspondence to Thilo Stehle or Terence S. Dermody.

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Glossary

Glycans

A nonspecific term for a polysaccharide or polymeric carbohydrate.

α-linked

A term used to describe a Neu5Ac that is incorporated into a polysaccharide via a glycosidic bond in which the alpha anomer, or C1 carbon, of Neu5Ac is in the axial position on the opposite side of the plane of the C6 carbon.

Lectins

Proteins, usually of plant origin, that bind to carbohydrates on the surface of animal cells; they also agglutinate red blood cells.

Neuraminidases

Enzymes, usually of microbial origin, that catalyse the removal of terminal sialic acids on the surface of cells or microorganisms.

Gangliosides

A type of glycolipid, commonly composed of a ceramide tail and a glycan portion that contains at least one sialic acid moiety.

Serotypes

A subclassification of a virus species that shares antigens and for which antibodies are cross-reactive.

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Stencel-Baerenwald, J., Reiss, K., Reiter, D. et al. The sweet spot: defining virus–sialic acid interactions. Nat Rev Microbiol 12, 739–749 (2014). https://doi.org/10.1038/nrmicro3346

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