Serum Amyloid P Component Binds to Influenza A Virus Haemagglutinin and Inhibits the Virus Infection In Vitro

• Published in: Scandinavian journal of immunology 1997-10, Vol.46 (4), p.331-337
• Main Authors: ANDERSEN, O., VILSGAARD RAVN, K., JUUL SØRENSEN, I., JONSON, G., HOLM NIELSEN, E., SVEHAG, S.‐E.
• Format: Article
• Language: English
• Subjects: Acetylgalactosamine - pharmacology; Animals; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Blotting, Western; Cell Line; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Dogs; Glycosaminoglycans - pharmacology; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Hemagglutinins, Viral - drug effects; Hemagglutinins, Viral - metabolism; Humans; influenza A virus; Influenza A virus - drug effects; Influenza A virus - metabolism; Influenza A virus - ultrastructure; Kidney; Monosaccharides - pharmacology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Protein Binding; Protein Denaturation; Serum Amyloid P-Component - metabolism; Serum Amyloid P-Component - physiology; Serum Amyloid P-Component - ultrastructure
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.1997.d01-147.x

Serum amyloid P component (SAP) is a member of the phylogenetically conserved and structurally related group of proteins called pentraxins. SAP exhibits multispecific calcium‐dependent binding to oligosaccharides with terminal N‐acetyl‐galactosamine, mannose and glucuronic acid. The authors report that SAP can bind to influenza A virus and inhibit agglutination of erythrocytes mediated by the virus subtypes H1N1, H2N2 and H3N2. SAP also inhibits the production of haemagglutinin (HA) and the cytopathogenic effect of influenza A virus in MDCK cells. The binding of SAP to the virus requires physiological calcium concentrations and is blocked by specific SAP antibodies. Denaturated and renaturated SAP retained inhibition of HA. Electron microscopy shows Ca2+‐dependent binding of SAP to spikes on the viral envelope and immunoblotting indicates that SAP binds to a 50–55 kDa peptide corresponding to the mass of the HA1 peptide. Of several monosaccharides tested only D‐mannose interfered with SAP's inhibition of both HA and infectivity. The glycosaminoglycans heparan sulfate and heparin, which bind SAP, reduced SAPs binding to the virus. The results indicate that the inhibition by SAP is due to steric effects when SAP binds to terminal mannose on oligosaccharides localized close to the sialic acid‐binding site of the HA trimer.