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HIV-inhibitory natural products part 71 - Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner

  1. Author:
    Bolmstedt, A. J.
    O'Keefe, B. R.
    Shenoy, S. R.
    McMahon, J. B.
    Boyd, M. R.

  2. Author Address

    NCI, Lab Drug Discovery Res & Dev, Div Basic Sci, Bldg 1052, Rm 121, Frederick, MD 21702 USA. NCI, Lab Drug Discovery Res & Dev, Div Basic Sci, Frederick, MD 21702 USA. Gothenburg Univ, Dept Clin Virol, S-41124 Gothenburg, Sweden. Boyd MR NCI, Lab Drug Discovery Res & Dev, Div Basic Sci, Bldg 1052, Rm 121, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Molecular Pharmacology
    1. 59
    2. 5
    3. Pages: 949-954
  4. Type of Article: Article
  1. Abstract:

    Herein we report that the novel HIV-inactivating protein cyanovirin-N (CV-N) targets specific, N-linked high-mannose oligosaccharides found on the viral envelope of HIV-1. First, we released the oligosaccharides by PnGase-treatment of HIV- gp120 (containing high-mannose, hybrid-type and complex-type oligosaccharides) or HSV-1 gC (containing only complex-type). Then, in an affinity chromatographic system, we found that CV-N bound to the free oligosaccharides from gp120 but not from gC- 1, suggesting that high-mannose oligosaccharides constitute a target structure for CV-N. This was supported by the affinity of CV-N for high-mannose glycans released from gp120 by endo-H as well as high-mannose glycans released from castanospermine- treated HSV-1 gC. Furthermore, free Man-8 or Man-9 oligosaccharides partially inhibited the binding of CV-N to gp120, although neither oligosaccharides smaller than Man-7 nor monosaccharides interfered with CV-N/gp120 interaction, thereby establishing the oligosaccharide-specific affinity of CV-N to high-mannose glycans. This affinity for high-mannose oligosaccharides may explain the broad antiviral activity of CV-N against human and primate immunodeficiency retroviruses as well as certain other viruses that carry these oligosaccharides.

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