Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development.
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.
Boyd
M R
MR
Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, Maryland 21702-1201, USA. boyd@dtpax2.ncifcrf.gov
Gustafson
K R
KR
McMahon
J B
JB
Shoemaker
R H
RH
O'Keefe
B R
BR
Mori
T
T
Gulakowski
R J
RJ
Wu
L
L
Rivera
M I
MI
Laurencot
C M
CM
Currens
M J
MJ
Cardellina
J H
JH
Buckheit
R W
RW
Nara
P L
PL
Pannell
L K
LK
Sowder
R C
RC
Henderson
L E
LE
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
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; C107733:cyanovirin N