1887

Abstract

Mannose-binding lectin (MBL), a serum lectin that mediates innate immune functions including activation of the lectin complement pathway, binds to carbohydrates expressed on some viral glycoproteins. In this study, the ability of MBL to bind to virus particles pseudotyped with Ebola and Marburg envelope glycoproteins was evaluated. Virus particles bearing either Ebola (Zaire strain) or Marburg (Musoke strain) envelope glycoproteins bound at significantly higher levels to immobilized MBL compared with virus particles pseudotyped with vesicular stomatitis virus glycoprotein or with no virus glycoprotein. As observed in previous studies, Ebola-pseudotyped virus bound to cells expressing the lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin). However, pre-incubation of virus with MBL blocked DC-SIGN-mediated binding to cells, suggesting that the two lectins bind at the same or overlapping sites on the Ebola glycoprotein. Neutralization experiments showed that virus pseudotyped with Ebola or Marburg (Musoke) glycoprotein was neutralized by complement, while the Marburg (Ravn strain) glycoprotein-pseudotyped virus was less sensitive to neutralization. Neutralization was partially mediated through the lectin complement pathway, since a complement source deficient in MBL was significantly less effective at neutralizing viruses pseudotyped with filovirus glycoproteins and addition of purified MBL to the MBL-deficient complement increased neutralization. These experiments demonstrated that MBL binds to filovirus envelope glycoproteins resulting in important biological effects and suggest that MBL can interact with filoviruses during infection in humans.

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2005-09-01
2019-10-22
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References

  1. Alvarez, C. P., Lasala, F., Carrillo, J., Muniz, O., Corbi, A. L. & Delgado, R. ( 2002; ). C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol 76, 6841–6844.[CrossRef]
    [Google Scholar]
  2. Anders, E. M., Hartley, C. A., Reading, P. C. & Ezekowitz, R. A. ( 1994; ). Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin. J Gen Virol 75, 615–622.[CrossRef]
    [Google Scholar]
  3. Baribaud, F., Pohlmann, S., Leslie, G., Mortari, F. & Doms, R. W. ( 2002; ). Quantitative expression and virus transmission analysis of DC-SIGN on monocyte-derived dendritic cells. J Virol 76, 9135–9142.[CrossRef]
    [Google Scholar]
  4. Baron, S., Singh, I., Chopra, A., Coppenhaver, D. & Pan, J. ( 2000; ). Innate antiviral defenses in body fluids and tissues. Antiviral Res 48, 71–89.[CrossRef]
    [Google Scholar]
  5. Barrientos, L. G., O'Keefe, B. R., Bray, M., Sanchez, A., Gronenborn, A. M. & Boyd, M. R. ( 2003; ). Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58, 47–56.[CrossRef]
    [Google Scholar]
  6. Barrientos, L. G., Lasala, F., Delgado, R., Sanchez, A. & Gronenborn, A. M. ( 2004a; ). Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity. Structure 12, 1799–1807.[CrossRef]
    [Google Scholar]
  7. Barrientos, L. G., Lasala, F., Otero, J. R., Sanchez, A. & Delgado, R. ( 2004b; ). In vitro evaluation of cyanovirin-N antiviral activity, by use of lentiviral vectors pseudotyped with filovirus envelope glycoproteins. J Infect Dis 189, 1440–1443.[CrossRef]
    [Google Scholar]
  8. Bashirova, A. A., Geijtenbeek, T. B., van Duijnhoven, G. C. & 10 other authors ( 2001; ). A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med 193, 671–678.[CrossRef]
    [Google Scholar]
  9. Basler, C. F., Wang, X., Muhlberger, E., Volchkov, V., Paragas, J., Klenk, H. D., Garcia-Sastre, A. & Palese, P. ( 2000; ). The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A 97, 12289–12294.[CrossRef]
    [Google Scholar]
  10. Basler, C. F., Mikulasova, A., Martinez-Sobrido, L., Paragas, J., Muhlberger, E., Bray, M., Klenk, H. D., Palese, P. & Garcia-Sastre, A. ( 2003; ). The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77, 7945–7956.[CrossRef]
    [Google Scholar]
  11. Beebe, D. P. & Cooper, N. R. ( 1981; ). Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum. J Immunol 126, 1562–1568.
    [Google Scholar]
  12. Biron, C. A. ( 1998; ). Role of early cytokines, including alpha and beta interferons (IFN-α/β), in innate and adaptive immune responses to viral infections. Semin Immunol 10, 383–390.[CrossRef]
    [Google Scholar]
  13. Biron, C. A., Nguyen, K. B., Pien, G. C., Cousens, L. P. & Salazar-Mather, T. P. ( 1999; ). Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17, 189–220.[CrossRef]
    [Google Scholar]
  14. Bolmstedt, A. J., O'Keefe, B. R., Shenoy, S. R., McMahon, J. B. & Boyd, M. R. ( 2001; ). Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner. Mol Pharmacol 59, 949–954.
    [Google Scholar]
  15. Botos, I. & Wlodawer, A. ( 2003; ). Cyanovirin-N: a sugar-binding antiviral protein with a new twist. Cell Mol Life Sci 60, 277–287.[CrossRef]
    [Google Scholar]
  16. Bray, M. ( 2001; ). The role of the Type I interferon response in the resistance of mice to filovirus infection. J Gen Virol 82, 1365–1373.
    [Google Scholar]
  17. Chan, S. Y., Speck, R. F., Ma, M. C. & Goldsmith, M. A. ( 2000; ). Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. J Virol 74, 4933–4937.[CrossRef]
    [Google Scholar]
  18. Coll, J. M. ( 1995; ). The glycoprotein G of rhabdoviruses. Arch Virol 140, 827–851.[CrossRef]
    [Google Scholar]
  19. DePolo, N. J., Reed, J. D., Sheridan, P. L., Townsend, K., Sauter, S. L., Jolly, D. J. & Dubensky, T. W., Jr ( 2000; ). VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum. Mol Ther 2, 218–222.[CrossRef]
    [Google Scholar]
  20. Esser, M. T., Mori, T., Mondor, I., Sattentau, Q. J., Dey, B., Berger, E. A., Boyd, M. R. & Lifson, J. D. ( 1999; ). Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J Virol 73, 4360–4371.
    [Google Scholar]
  21. Ezekowitz, R. A. ( 2003; ). Role of the mannose-binding lectin in innate immunity. J Infect Dis 187, S335–S339.[CrossRef]
    [Google Scholar]
  22. Ezekowitz, R. A., Kuhlman, M., Groopman, J. E. & Byrn, R. A. ( 1989; ). A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med 169, 185–196.[CrossRef]
    [Google Scholar]
  23. Feinberg, H., Mitchell, D. A., Drickamer, K. & Weis, W. I. ( 2001; ). Structural basis for selective recognition of oligosaccharides by DC- SIGN and DC-SIGNR. Science 294, 2163–2166.[CrossRef]
    [Google Scholar]
  24. Feldmann, H., Nichol, S. T., Klenk, H. D., Peters, C. J. & Sanchez, A. ( 1994; ). Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein. Virology 199, 469–473.[CrossRef]
    [Google Scholar]
  25. Gadjeva, M., Paludan, S. R., Thiel, S. & 8 other authors ( 2004; ). Mannan-binding lectin modulates the response to HSV-2 infection. Clin Exp Immunol 138, 304–311.[CrossRef]
    [Google Scholar]
  26. Geijtenbeek, T. B., Kwon, D. S., Torensma, R. & 9 other authors ( 2000; ). DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells [see comments]. Cell 100, 587–597.[CrossRef]
    [Google Scholar]
  27. Geisbert, T. W., Hensley, L. E., Larsen, T. & 7 other authors ( 2003; ). Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163, 2347–2370.[CrossRef]
    [Google Scholar]
  28. Geyer, H., Will, C., Feldmann, H., Klenk, H. D. & Geyer, R. ( 1992; ). Carbohydrate structure of Marburg virus glycoprotein. Glycobiology 2, 299–312.[CrossRef]
    [Google Scholar]
  29. Hackett, C. J. ( 2003; ). Innate immune activation as a broad-spectrum biodefense strategy: prospects and research challenges. J Allergy Clin Immunol 112, 686–694.[CrossRef]
    [Google Scholar]
  30. Hansen, S. & Holmskov, U. ( 1998; ). Structural aspects of collectins and receptors for collectins. Immunobiology 199, 165–189.[CrossRef]
    [Google Scholar]
  31. Hart, M. L., Saifuddin, M., Uemura, K., Bremer, E. G., Hooker, B., Kawasaki, T. & Spear, G. T. ( 2002; ). High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. AIDS Res Hum Retroviruses 18, 1311–1317.[CrossRef]
    [Google Scholar]
  32. Hart, M. L., Saifuddin, M. & Spear, G. T. ( 2003; ). Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. J Gen Virol 84, 353–360.[CrossRef]
    [Google Scholar]
  33. Hartshorn, K. L., Sastry, K., White, M. R., Anders, E. M., Super, M., Ezekowitz, R. A. & Tauber, A. I. ( 1993; ). Human mannose-binding protein functions as an opsonin for influenza A viruses. J Clin Invest 91, 1414–1420.[CrossRef]
    [Google Scholar]
  34. Hartshorn, K. L., White, M. R., Shepherd, V., Reid, K., Jensenius, J. C. & Crouch, E. C. ( 1997; ). Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol 273, L1156–L1166.
    [Google Scholar]
  35. Haurum, J. S., Thiel, S., Jones, I. M., Fischer, P. B., Laursen, S. B. & Jensenius, J. C. ( 1993; ). Complement activation upon binding of mannan-binding protein to HIV envelope glycoproteins. AIDS 7, 1307–1313.[CrossRef]
    [Google Scholar]
  36. Hevey, M., Negley, D. & Schmaljohn, A. ( 2003; ). Characterization of monoclonal antibodies to Marburg virus (strain Musoke) glycoprotein and identification of two protective epitopes. Virology 314, 350–357.[CrossRef]
    [Google Scholar]
  37. Jack, D. L., Klein, N. J. & Turner, M. W. ( 2001; ). Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev 180, 86–99.[CrossRef]
    [Google Scholar]
  38. Ji, X., Gewurz, H. & Spear, G. T. ( 2005; ). Mannose binding lectin (MBL) and HIV. Mol Immunol 42, 145–152.[CrossRef]
    [Google Scholar]
  39. Lin, G., Simmons, G., Pohlmann, S. & 8 other authors ( 2003; ). Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol 77, 1337–1346.[CrossRef]
    [Google Scholar]
  40. Mahanty, S. & Bray, M. ( 2004; ). Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 4, 487–498.[CrossRef]
    [Google Scholar]
  41. Mahanty, S., Gupta, M., Paragas, J., Bray, M., Ahmed, R. & Rollin, P. E. ( 2003; ). Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection. Virology 312, 415–424.[CrossRef]
    [Google Scholar]
  42. Marzi, A., Gramberg, T., Simmons, G. & 12 other authors ( 2004; ). DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J Virol 78, 12090–12095.[CrossRef]
    [Google Scholar]
  43. Matsushita, M. & Fujita, T. ( 2001; ). Ficolins and the lectin complement pathway. Immunol Rev 180, 78–85.[CrossRef]
    [Google Scholar]
  44. Ohtani, K., Suzuki, Y., Eda, S. & 7 other authors ( 1999; ). High-level and effective production of human mannan-binding lectin (MBL) in Chinese hamster ovary (CHO) cells. J Immunol Methods 222, 135–144.[CrossRef]
    [Google Scholar]
  45. Petersen, S. V., Thiel, S. & Jensenius, J. C. ( 2001; ). The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 38, 133–149.[CrossRef]
    [Google Scholar]
  46. Reading, P. C., Hartley, C. A., Ezekowitz, R. A. & Anders, E. M. ( 1995; ). A serum mannose-binding lectin mediates complement-dependent lysis of influenza virus-infected cells. Biochem Biophys Res Commun 217, 1128–1136.[CrossRef]
    [Google Scholar]
  47. Reed, D. S., Hensley, L. E., Geisbert, J. B., Jahrling, P. B. & Geisbert, T. W. ( 2004; ). Depletion of peripheral blood T lymphocytes and NK cells during the course of Ebola hemorrhagic fever in cynomolgus macaques. Viral Immunol 17, 390–400.[CrossRef]
    [Google Scholar]
  48. Saifuddin, M., Hart, M. L., Gewurz, H., Zhang, Y. & Spear, G. T. ( 2000; ). Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1. J Gen Virol 81, 949–955.
    [Google Scholar]
  49. Sanchez, A., Trappier, S. G., Mahy, B. W., Peters, C. J. & Nichol, S. T. ( 1996; ). The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A 93, 3602–3607.[CrossRef]
    [Google Scholar]
  50. Sanchez, A., Lukwiya, M., Bausch, D., Mahanty, S., Sanchez, A. J., Wagoner, K. D. & Rollin, P. E. ( 2004; ). Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol 78, 10370–10377.[CrossRef]
    [Google Scholar]
  51. Simmons, G., Wool-Lewis, R. J., Baribaud, F., Netter, R. C. & Bates, P. ( 2002; ). Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence. J Virol 76, 2518–2528.[CrossRef]
    [Google Scholar]
  52. Simmons, G., Reeves, J. D., Grogan, C. C. & 10 other authors ( 2003; ). DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305, 115–123.[CrossRef]
    [Google Scholar]
  53. Singh, I. P. & Baron, S. ( 2000; ). Innate defences against viraemia. Rev Med Virol 10, 395–403.[CrossRef]
    [Google Scholar]
  54. Spear, G. T., Hart, M., Olinger, G. G., Hashemi, F. B. & Saifuddin, M. ( 2001; ). The role of the complement system in virus infections. Curr Top Microbiol Immunol 260, 229–245.
    [Google Scholar]
  55. Suankratay, C., Zhang, X. H., Zhang, Y., Lint, T. F. & Gewurz, H. ( 1998; ). Requirement for the alternative pathway as well as C4 and C2 in complement-dependent hemolysis via the lectin pathway. J Immunol 160, 3006–3013.
    [Google Scholar]
  56. Sullivan, N. J., Peterson, M., Yang, Z. Y., Kong, W. P., Duckers, H., Nabel, E. & Nabel, G. J. ( 2005; ). Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. J Virol 79, 547–553.[CrossRef]
    [Google Scholar]
  57. Takada, A. & Kawaoka, Y. ( 2001; ). The pathogenesis of Ebola hemorrhagic fever. Trends Microbiol 9, 506–511.[CrossRef]
    [Google Scholar]
  58. Takada, A. & Kawaoka, Y. ( 2003; ). Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 13, 387–398.[CrossRef]
    [Google Scholar]
  59. Takada, A., Feldmann, H., Ksiazek, T. G. & Kawaoka, Y. ( 2003; ). Antibody-dependent enhancement of Ebola virus infection. J Virol 77, 7539–7544.[CrossRef]
    [Google Scholar]
  60. Takada, A., Fujioka, K., Tsuiji, M. & 7 other authors ( 2004; ). Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol 78, 2943–2947.[CrossRef]
    [Google Scholar]
  61. Valdimarsson, H., Stefansson, M., Vikingsdottir, T., Arason, G. J., Koch, C., Thiel, S. & Jensenius, J. C. ( 1998; ). Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans. Scand J Immunol 48, 116–123.[CrossRef]
    [Google Scholar]
  62. Warfield, K. L., Perkins, J. G., Swenson, D. L., Deal, E. M., Bosio, C. M., Aman, M. J., Yokoyama, W. M., Young, H. A. & Bavari, S. ( 2004; ). Role of natural killer cells in innate protection against lethal Ebola virus infection. J Exp Med 200, 169–179.[CrossRef]
    [Google Scholar]
  63. Wilson, J. A., Hevey, M., Bakken, R., Guest, S., Bray, M., Schmaljohn, A. L. & Hart, M. K. ( 2000; ). Epitopes involved in antibody-mediated protection from Ebola virus. Science 287, 1664–1666.[CrossRef]
    [Google Scholar]
  64. Wu, L., Martin, T. D., Carrington, M. & KewalRamani, V. N. ( 2004; ). Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. Virology 318, 17–23.[CrossRef]
    [Google Scholar]
  65. Ying, H., Ji, X., Hart, M. L., Gupta, K., Saifuddin, M., Zariffard, M. R. & Spear, G. T. ( 2004; ). Interaction of mannose-binding lectin with HIV type 1 is sufficient for virus opsonization but not neutralization. AIDS Res Hum Retroviruses 20, 327–335.[CrossRef]
    [Google Scholar]
  66. Zabavichene, N. M. & Chepurnov, A. A. ( 2004; ). Dynamics of complement hemolytic activity in experimental Ebola infection. Vopr Virusol 49, 21–25 (in Russian).
    [Google Scholar]
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