title: Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Emma R
authors.initials: ER
authors.lastname: Job
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Brad
authors.initials: B
authors.lastname: Gilbertson
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edenborough
authors.forename: Lorena E
authors.initials: LE
authors.lastname: Brown
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D015922:Complement C1q / Q000378:metabolism; D004285:Dogs; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects / Q000378:metabolism*; D007251:Influenza, Human / Q000378:metabolism / Q000473:pathology / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D037601:Mannose-Binding Lectin / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D009500:Neutralization Tests; D011485:Protein Binding / Q000187:drug effects; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D013045:Species Specificity; D000099153:Pentraxins
chemical_list: D000998:Antiviral Agents; D002097:C-Reactive Protein; D002118:Calcium; D015922:Complement C1q; D037601:Mannose-Binding Lectin; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase; D037663:Pulmonary Surfactant-Associated Protein D; D011991:Receptors, Virus; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
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