Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity

Biochem J. 2000 Oct 15;351 Pt 2(Pt 2):449-58.

Abstract

Collectins are important in the initial containment of a variety of pathogens, including influenza A virus (IAV). We provide the first systematic evaluation of the oligosaccharide-binding sites for pulmonary surfactant protein D (SP-D) on specific IAV coat glycoproteins and define the relationship between this binding and antiviral activity. With the use of several techniques, SP-D was found to bind via its carbohydrate-recognition domain (CRD) to mannosylated, N-linked carbohydrates on the HA(1) domain of the haemagglutinin (HA) and on the neuraminidase of IAV. Using a set of IAV strains that differed in the level and site of glycosylation, and a panel of recombinant collectins, we found that binding of SP-D to the globular domain of the HA was critical in mediating the inhibition of viral haemagglutination activity and infectivity. We also demonstrated that the pattern of binding of a collectin to IAV glycoproteins can be modified by altering the monosaccharide-binding affinity of its CRD or by linking the CRD to a different N-terminal/collagen domain. These studies clarify the mechanisms of viral neutralization by collectins and might be useful in engineering collectins for enhanced antiviral activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidohydrolases / metabolism
  • Animals
  • Blotting, Western
  • Capsid / metabolism
  • Carbohydrate Metabolism
  • Cattle
  • Cell Line
  • DNA, Complementary / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Glycoproteins / metabolism*
  • Glycosylation
  • Hemagglutinins / metabolism*
  • Influenza A virus / metabolism*
  • Neuraminidase / metabolism
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Protein Binding
  • Protein Structure, Tertiary
  • Pulmonary Surfactant-Associated Protein D
  • Pulmonary Surfactants / metabolism*
  • Recombinant Proteins / metabolism

Substances

  • DNA, Complementary
  • Glycoproteins
  • Hemagglutinins
  • Pulmonary Surfactant-Associated Protein D
  • Pulmonary Surfactants
  • Recombinant Proteins
  • Neuraminidase
  • Amidohydrolases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase