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.
Footnotes
- Received October 30, 2000.
- Accepted January 17, 2001.
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Send reprint requests to: Dr. Michael R. Boyd, Laboratory of Drug Discovery Research and Development, Division of Basic Sciences, National Cancer Institute-Frederick, Bldg. 1052, Rm. 121, Frederick, MD 21702-1201. E-mail: boyd{at}dtpax2.ncifcrf.gov
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This work was supported in part by grants from the Swedish Medical Research Council (Grants 9083 and 10437), the National Swedish Board for Technical Development (Project 87–0256P), and the Medical Faculty, University of Göteborg.
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This article constitutes part 71 in the National Cancer Institute Laboratory of Drug Discovery Research and Development series “HIV-Inhibitory Natural Products”; for part 70 see Bokesch HR, Pannell LK, Cochran PK, Sowder RC II, McKee TC and Boyd MR (2001) A novel anti-HIV macrocyclic peptide from Palcourea condensata. J Nat Prod 64:249–250.
- The American Society for Pharmacology and Experimental Therapeutics
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