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

Boyd, M.R., Gustafson, K.R., McMahon, J.B., Shoemaker, R.H., O'Keefe, B.R., Mori, T., Gulakowski, R.J., Wu, L., Rivera, M., Laurencot, C.M., Cardellina, J.H., II, Buckheit, R.W., Nara, P.L., Pannell, L.K., Sowder, R.C., II, Henderson, L.E. Antimicrob. Agents Chemother. 41: 1521-1530, 1997.

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 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, futher enhancing its potential as an anti-HIV microbicide.

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