1. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development.
- Author
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Boyd MR, Gustafson KR, McMahon JB, Shoemaker RH, O'Keefe BR, Mori T, Gulakowski RJ, Wu L, Rivera MI, Laurencot CM, Currens MJ, Cardellina JH 2nd, Buckheit RW Jr, Nara PL, Pannell LK, Sowder RC 2nd, and Henderson LE
- Subjects
- Acquired Immunodeficiency Syndrome transmission, Amino Acid Sequence, Anti-HIV Agents chemistry, Anti-HIV Agents metabolism, Base Sequence, Carrier Proteins chemistry, Carrier Proteins metabolism, Cell Fusion, Cell Survival drug effects, Enzyme-Linked Immunosorbent Assay, Humans, Molecular Sequence Data, Molecular Weight, Protein Binding, Recombinant Proteins chemistry, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Titrimetry, Ultrafiltration, Anti-HIV Agents isolation & purification, Bacterial Proteins, Carrier Proteins isolation & purification, HIV Envelope Protein gp120 metabolism
- Abstract
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.
- Published
- 1997
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