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. 2000 Oct 15;351(Pt 2):449–458.

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

K L Hartshorn 1, M R White 1, D R Voelker 1, J Coburn 1, K Zaner 1, E C Crouch 1
PMCID: PMC1221381  PMID: 11023831

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.

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Selected References

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  1. Alexander-Miller M. A., Burke K., Koszinowski U. H., Hansen T. H., Connolly J. M. Alloreactive cytotoxic T lymphocytes generated in the presence of viral-derived peptides show exquisite peptide and MHC specificity. J Immunol. 1993 Jul 1;151(1):1–10. [PubMed] [Google Scholar]
  2. Anders E. M., Hartley C. A., Jackson D. C. Bovine and mouse serum beta inhibitors of influenza A viruses are mannose-binding lectins. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4485–4489. doi: 10.1073/pnas.87.12.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barka N., Tomasi J. P., Stadtsbaeder S. Use of whole Streptococcus pneumoniae cells as a solid phase sorbent for C-reactive protein measurement by ELISA. J Immunol Methods. 1985 Sep 3;82(1):57–63. doi: 10.1016/0022-1759(85)90224-8. [DOI] [PubMed] [Google Scholar]
  4. Benne C. A., Kraaijeveld C. A., van Strijp J. A., Brouwer E., Harmsen M., Verhoef J., van Golde L. M., van Iwaarden J. F. Interactions of surfactant protein A with influenza A viruses: binding and neutralization. J Infect Dis. 1995 Feb;171(2):335–341. doi: 10.1093/infdis/171.2.335. [DOI] [PubMed] [Google Scholar]
  5. Brown-Augsburger P., Chang D., Rust K., Crouch E. C. Biosynthesis of surfactant protein D. Contributions of conserved NH2-terminal cysteine residues and collagen helix formation to assembly and secretion. J Biol Chem. 1996 Aug 2;271(31):18912–18919. doi: 10.1074/jbc.271.31.18912. [DOI] [PubMed] [Google Scholar]
  6. Caton A. J., Brownlee G. G., Yewdell J. W., Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982 Dec;31(2 Pt 1):417–427. doi: 10.1016/0092-8674(82)90135-0. [DOI] [PubMed] [Google Scholar]
  7. Crouch E., Chang D., Rust K., Persson A., Heuser J. Recombinant pulmonary surfactant protein D. Post-translational modification and molecular assembly. J Biol Chem. 1994 Jun 3;269(22):15808–15813. [PubMed] [Google Scholar]
  8. Crouch E., Hartshorn K., Ofek I. Collectins and pulmonary innate immunity. Immunol Rev. 2000 Feb;173:52–65. doi: 10.1034/j.1600-065x.2000.917311.x. [DOI] [PubMed] [Google Scholar]
  9. Daigneault D. E., Hartshorn K. L., Liou L. S., Abbruzzi G. M., White M. R., Oh S. K., Tauber A. I. Influenza A virus binding to human neutrophils and cross-linking requirements for activation. Blood. 1992 Dec 15;80(12):3227–3234. [PubMed] [Google Scholar]
  10. Fischer P. B., Ellermann-Eriksen S., Thiel S., Jensenius J. C., Mogensen S. C. Mannan-binding protein and bovine conglutinin mediate enhancement of herpes simplex virus type 2 infection in mice. Scand J Immunol. 1994 May;39(5):439–445. doi: 10.1111/j.1365-3083.1994.tb03398.x. [DOI] [PubMed] [Google Scholar]
  11. Hartley C. A., Jackson D. C., Anders E. M. Two distinct serum mannose-binding lectins function as beta inhibitors of influenza virus: identification of bovine serum beta inhibitor as conglutinin. J Virol. 1992 Jul;66(7):4358–4363. doi: 10.1128/jvi.66.7.4358-4363.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hartshorn K. L., Collamer M., Auerbach M., Myers J. B., Pavlotsky N., Tauber A. I. Effects of influenza A virus on human neutrophil calcium metabolism. J Immunol. 1988 Aug 15;141(4):1295–1301. [PubMed] [Google Scholar]
  13. Hartshorn K. L., Crouch E. C., White M. R., Eggleton P., Tauber A. I., Chang D., Sastry K. Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest. 1994 Jul;94(1):311–319. doi: 10.1172/JCI117323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hartshorn K. L., Sastry K. N., Chang D., White M. R., Crouch E. C. Enhanced anti-influenza activity of a surfactant protein D and serum conglutinin fusion protein. Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L90–L98. doi: 10.1152/ajplung.2000.278.1.L90. [DOI] [PubMed] [Google Scholar]
  15. Hartshorn K. L., Sastry K., White M. R., Anders E. M., Super M., Ezekowitz R. A., Tauber A. I. Human mannose-binding protein functions as an opsonin for influenza A viruses. J Clin Invest. 1993 Apr;91(4):1414–1420. doi: 10.1172/JCI116345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hartshorn K. L., White M. R., Shepherd V., Reid K., Jensenius J. C., Crouch E. C. Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol. 1997 Dec;273(6 Pt 1):L1156–L1166. doi: 10.1152/ajplung.1997.273.6.L1156. [DOI] [PubMed] [Google Scholar]
  17. Hartshorn K., Chang D., Rust K., White M., Heuser J., Crouch E. Interactions of recombinant human pulmonary surfactant protein D and SP-D multimers with influenza A. Am J Physiol. 1996 Nov;271(5 Pt 1):L753–L762. doi: 10.1152/ajplung.1996.271.5.L753. [DOI] [PubMed] [Google Scholar]
  18. Holmskov U., Malhotra R., Sim R. B., Jensenius J. C. Collectins: collagenous C-type lectins of the innate immune defense system. Immunol Today. 1994 Feb;15(2):67–74. doi: 10.1016/0167-5699(94)90136-8. [DOI] [PubMed] [Google Scholar]
  19. Kase T., Suzuki Y., Kawai T., Sakamoto T., Ohtani K., Eda S., Maeda A., Okuno Y., Kurimura T., Wakamiya N. Human mannan-binding lectin inhibits the infection of influenza A virus without complement. Immunology. 1999 Jul;97(3):385–392. doi: 10.1046/j.1365-2567.1999.00781.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee Y. M., Leiby K. R., Allar J., Paris K., Lerch B., Okarma T. B. Primary structure of bovine conglutinin, a member of the C-type animal lectin family. J Biol Chem. 1991 Feb 15;266(5):2715–2723. [PubMed] [Google Scholar]
  21. Liou L. S., Sastry R., Hartshorn K. L., Lee Y. M., Okarma T. B., Tauber A. I., Sastry K. N. Bovine conglutinin (BC) mRNA expressed in liver: cloning and characterization of the BC cDNA reveals strong homology to surfactant protein-D. Gene. 1994 Apr 20;141(2):277–281. doi: 10.1016/0378-1119(94)90585-1. [DOI] [PubMed] [Google Scholar]
  22. Malhotra R., Haurum J. S., Thiel S., Sim R. B. Binding of human collectins (SP-A and MBP) to influenza virus. Biochem J. 1994 Dec 1;304(Pt 2):455–461. doi: 10.1042/bj3040455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ogasawara Y., Voelker D. R. Altered carbohydrate recognition specificity engineered into surfactant protein D reveals different binding mechanisms for phosphatidylinositol and glucosylceramide. J Biol Chem. 1995 Jun 16;270(24):14725–14732. doi: 10.1074/jbc.270.24.14725. [DOI] [PubMed] [Google Scholar]
  24. Reading P. C., Morey L. S., Crouch E. C., Anders E. M. Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J Virol. 1997 Nov;71(11):8204–8212. doi: 10.1128/jvi.71.11.8204-8212.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schwarz R. T., Klenk H. D. Carbohydrates of influenza virus. IV. Strain-dependent variations. Virology. 1981 Sep;113(2):584–593. doi: 10.1016/0042-6822(81)90186-0. [DOI] [PubMed] [Google Scholar]
  26. Skehel J. J., Stevens D. J., Daniels R. S., Douglas A. R., Knossow M., Wilson I. A., Wiley D. C. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1779–1783. doi: 10.1073/pnas.81.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. White M. R., Crouch E., Chang D., Sastry K., Guo N., Engelich G., Takahashi K., Ezekowitz R. A., Hartshorn K. L. Enhanced antiviral and opsonic activity of a human mannose-binding lectin and surfactant protein D chimera. J Immunol. 2000 Aug 15;165(4):2108–2115. doi: 10.4049/jimmunol.165.4.2108. [DOI] [PubMed] [Google Scholar]

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