Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses

PLoS One. 2013;8(3):e59623. doi: 10.1371/journal.pone.0059623. Epub 2013 Mar 27.


Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / metabolism*
  • Antiviral Agents / pharmacology
  • C-Reactive Protein / metabolism
  • Calcium / pharmacology
  • Complement C1q / metabolism
  • Dogs
  • Hemagglutination Inhibition Tests
  • Humans
  • Hydrolysis / drug effects
  • Influenza A virus / drug effects
  • Influenza A virus / metabolism*
  • Influenza, Human / metabolism
  • Influenza, Human / pathology
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Mannose-Binding Lectin / metabolism
  • Mutation / genetics
  • N-Acetylneuraminic Acid / metabolism*
  • Neuraminidase / metabolism
  • Neutralization Tests
  • Protein Binding / drug effects
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Receptors, Virus / metabolism
  • Serum Amyloid P-Component / metabolism*
  • Species Specificity


  • Antiviral Agents
  • Mannose-Binding Lectin
  • Pulmonary Surfactant-Associated Protein D
  • Receptors, Virus
  • Serum Amyloid P-Component
  • PTX3 protein
  • Complement C1q
  • C-Reactive Protein
  • Neuraminidase
  • N-Acetylneuraminic Acid
  • Calcium

Grant support

This work was supported by Project Grant #1032079 from the National Health and Medical Research Council (NHMRC) of Australia. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing. The financial support of the European Research Council (ERC project HIIS) and of the European Commission (FP7-HEALTH-2011-ADITEC-280873) is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.