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Antimicrobial Agents and Chemotherapy, Jul 1997, 1521-1530, Vol 41, No. 7
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Discovery of cyanovirin-N, a novel human immunodeficiency virus- inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development

MR Boyd, KR Gustafson, JB McMahon, RH Shoemaker, BR O'Keefe, T Mori, RJ Gulakowski, L Wu, MI Rivera, CM Laurencot, MJ Currens, JH Cardellina 2nd, RW Buckheit Jr, PL Nara, LK Pannell, RC Sowder 2nd and LE Henderson
Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201, USA. boyd@dtpax2.ncifcrf.gov

We have isolated and sequenced a novel 11-kDa virucidal protein, named cyanovirin-N (CV-N), from cultures of the cyanobacterium (blue-green alga) Nostoc ellipsosporum. We also have produced CV-N recombinantly by expression of a corresponding DNA sequence in Escherichia coli. Low nanomolar concentrations of either natural or recombinant CV-N irreversibly inactivate diverse laboratory strains and primary isolates of human immunodeficiency virus (HIV) type 1 as well as strains of HIV type 2 and simian immunodeficiency virus. In addition, CV-N aborts cell- to-cell fusion and transmission of HIV-1 infection. Continuous, 2-day exposures of uninfected CEM-SS cells or peripheral blood lymphocytes to high concentrations (e.g., 9,000 nM) of CV-N were not lethal to these representative host cell types. The antiviral activity of CV-N is due, at least in part, to unique, high-affinity interactions of CV-N with the viral surface envelope glycoprotein gp120. The biological activity of CV-N is highly resistant to physicochemical denaturation, further enhancing its potential as an anti-HIV microbicide.


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