Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner.
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.
Bolmstedt
A J
AJ
Department of Clinical Virology, University of Göteborg, Sweden.
O'Keefe
B R
BR
Shenoy
S R
SR
McMahon
J B
JB
Boyd
M R
MR
D000998:Antiviral Agents / Q000494:pharmacology*; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000187:drug effects / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D008358:Mannose / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011134:Polysaccharides / Q000378:metabolism*
D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; C107733:cyanovirin N; D008358:Mannose