title: Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development.
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.
authors.affiliation: Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201, USA. boyd@dtpax2.ncifcrf.gov
authors.forename: M R
authors.initials: MR
authors.lastname: Boyd
authors.forename: K R
authors.initials: KR
authors.lastname: Gustafson
authors.forename: J B
authors.initials: JB
authors.lastname: McMahon
authors.forename: R H
authors.initials: RH
authors.lastname: Shoemaker
authors.forename: B R
authors.initials: BR
authors.lastname: O'Keefe
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: R J
authors.initials: RJ
authors.lastname: Gulakowski
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: M I
authors.initials: MI
authors.lastname: Rivera
authors.forename: C M
authors.initials: CM
authors.lastname: Laurencot
authors.forename: M J
authors.initials: MJ
authors.lastname: Currens
authors.forename: J H
authors.initials: JH
authors.lastname: Cardellina
authors.forename: R W
authors.initials: RW
authors.lastname: Buckheit
authors.forename: P L
authors.initials: PL
authors.lastname: Nara
authors.forename: L K
authors.initials: LK
authors.lastname: Pannell
authors.forename: R C
authors.initials: RC
authors.lastname: Sowder
authors.forename: L E
authors.initials: LE
authors.lastname: Henderson
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000635:transmission; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D001426:Bacterial Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D002459:Cell Fusion; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017186:Titrimetry; D014462:Ultrafiltration
chemical_list: D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; C107733:cyanovirin N