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Antimicrob Agents Chemother. 1997 Jul; 41(7): 1521–1530.
PMCID: PMC163952

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.

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These references are in PubMed. This may not be the complete list of references from this article.
  • Andreu A, Stapleton AE, Fennell CL, Hillier SL, Stamm WE. Hemagglutination, adherence, and surface properties of vaginal Lactobacillus species. J Infect Dis. 1995 May;171(5):1237–1243. [PubMed]
  • Balter M. UN readies new global AIDS plan. Science. 1994 Nov 25;266(5189):1312–1313. [PubMed]
  • Barbas CF, 3rd, Björling E, Chiodi F, Dunlop N, Cababa D, Jones TM, Zebedee SL, Persson MA, Nara PL, Norrby E, et al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9339–9343. [PMC free article] [PubMed]
  • Bates P. Chemokine receptors and HIV-1: an attractive pair? Cell. 1996 Jul 12;86(1):1–3. [PubMed]
  • Byrn RA, Sekigawa I, Chamow SM, Johnson JS, Gregory TJ, Capon DJ, Groopman JE. Characterization of in vitro inhibition of human immunodeficiency virus by purified recombinant CD4. J Virol. 1989 Oct;63(10):4370–4375. [PMC free article] [PubMed]
  • Buckheit RW, Jr, Fliakas-Boltz V, Decker WD, Roberson JL, Pyle CA, White EL, Bowdon BJ, McMahon JB, Boyd MR, Bader JP, et al. Biological and biochemical anti-HIV activity of the benzothiadiazine class of nonnucleoside reverse transcriptase inhibitors. Antiviral Res. 1994 Sep;25(1):43–56. [PubMed]
  • Buckheit RW, Jr, Roberson JL, Lackman-Smith C, Wyatt JR, Vickers TA, Ecker DJ. Potent and specific inhibition of HIV envelope-mediated cell fusion and virus binding by G quartet-forming oligonucleotide (ISIS 5320). AIDS Res Hum Retroviruses. 1994 Nov;10(11):1497–1506. [PubMed]
  • Burton DR, Barbas CF, 3rd, Persson MA, Koenig S, Chanock RM, Lerner RA. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134–10137. [PMC free article] [PubMed]
  • Burton DR, Pyati J, Koduri R, Sharp SJ, Thornton GB, Parren PW, Sawyer LS, Hendry RM, Dunlop N, Nara PL, et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science. 1994 Nov 11;266(5187):1024–1027. [PubMed]
  • Cardellina JH, 2nd, Munro MH, Fuller RW, Manfredi KP, McKee TC, Tischler M, Bokesch HR, Gustafson KR, Beutler JA, Boyd MR. A chemical screening strategy for the dereplication and prioritization of HIV-inhibitory aqueous natural products extracts. J Nat Prod. 1993 Jul;56(7):1123–1129. [PubMed]
  • Chackerian B, Long EM, Luciw PA, Overbaugh J. Human immunodeficiency virus type 1 coreceptors participate in postentry stages in the virus replication cycle and function in simian immunodeficiency virus infection. J Virol. 1997 May;71(5):3932–3939. [PMC free article] [PubMed]
  • Chang H. Genetic engineering to enhance microbial interference and related therapeutic applications. Nat Biotechnol. 1996 Apr;14(4):444–447. [PubMed]
  • Chen Z, Zhou P, Ho DD, Landau NR, Marx PA. Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J Virol. 1997 Apr;71(4):2705–2714. [PMC free article] [PubMed]
  • Ciminale V, Felber BK, Campbell M, Pavlakis GN. A bioassay for HIV-1 based on Env-CD4 interaction. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1281–1287. [PubMed]
  • Cohen J. Exploiting the HIV-chemokine nexus. Science. 1997 Feb 28;275(5304):1261–1264. [PubMed]
  • Collman R, Balliet JW, Gregory SA, Friedman H, Kolson DL, Nathanson N, Srinivasan A. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992 Dec;66(12):7517–7521. [PMC free article] [PubMed]
  • Currens MJ, Gulakowski RJ, Mariner JM, Moran RA, Buckheit RW, Jr, Gustafson KR, McMahon JB, Boyd MR. Antiviral activity and mechanism of action of calanolide A against the human immunodeficiency virus type-1. J Pharmacol Exp Ther. 1996 Nov;279(2):645–651. [PubMed]
  • Currens MJ, Mariner JM, McMahon JB, Boyd MR. Kinetic analysis of inhibition of human immunodeficiency virus type-1 reverse transcriptase by calanolide A. J Pharmacol Exp Ther. 1996 Nov;279(2):652–661. [PubMed]
  • Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996 Sep 27;273(5283):1856–1862. [PubMed]
  • D'Souza MP, Durda P, Hanson CV, Milman G. Evaluation of monoclonal antibodies to HIV-1 by neutralization and serological assays: an international collaboration. Collaborating Investigators. AIDS. 1991 Sep;5(9):1061–1070. [PubMed]
  • Elmer GW, Surawicz CM, McFarland LV. Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA. 1996 Mar 20;275(11):870–876. [PubMed]
  • Endres MJ, Clapham PR, Marsh M, Ahuja M, Turner JD, McKnight A, Thomas JF, Stoebenau-Haggarty B, Choe S, Vance PJ, et al. CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell. 1996 Nov 15;87(4):745–756. [PubMed]
  • Essex M. Retroviral vaccines: challenges for the developing world. AIDS Res Hum Retroviruses. 1996 Mar 20;12(5):361–363. [PubMed]
  • Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. [PubMed]
  • Gendelman HE, Orenstein JM, Baca LM, Weiser B, Burger H, Kalter DC, Meltzer MS. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. [PubMed]
  • Gorny MK, Xu JY, Gianakakos V, Karwowska S, Williams C, Sheppard HW, Hanson CV, Zolla-Pazner S. Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3238–3242. [PMC free article] [PubMed]
  • Gorny MK, Xu JY, Karwowska S, Buchbinder A, Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol. 1993 Jan 15;150(2):635–643. [PubMed]
  • Gulakowski RJ, McMahon JB, Staley PG, Moran RA, Boyd MR. A semiautomated multiparameter approach for anti-HIV drug screening. J Virol Methods. 1991 Jun;33(1-2):87–100. [PubMed]
  • Gustafson KR, Cardellina JH, 2nd, Fuller RW, Weislow OS, Kiser RF, Snader KM, Patterson GM, Boyd MR. AIDS-antiviral sulfolipids from cyanobacteria (blue-green algae). J Natl Cancer Inst. 1989 Aug 16;81(16):1254–1258. [PubMed]
  • Hols P, Ferain T, Garmyn D, Bernard N, Delcour J. Use of homologous expression-secretion signals and vector-free stable chromosomal integration in engineering of Lactobacillus plantarum for alpha-amylase and levanase expression. Appl Environ Microbiol. 1994 May;60(5):1401–1413. [PMC free article] [PubMed]
  • Kelley KJ. Using host defenses to fight infectious diseases. Nat Biotechnol. 1996 May;14(5):587–590. [PubMed]
  • Kimpton J, Emerman M. Detection of replication-competent and pseudotyped human immunodeficiency virus with a sensitive cell line on the basis of activation of an integrated beta-galactosidase gene. J Virol. 1992 Apr;66(4):2232–2239. [PMC free article] [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Laman JD, Schellekens MM, Abacioglu YH, Lewis GK, Tersmette M, Fouchier RA, Langedijk JP, Claassen E, Boersma WJ. Variant-specific monoclonal and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. J Virol. 1992 Mar;66(3):1823–1831. [PMC free article] [PubMed]
  • Laman JD, Schellekens MM, Lewis GK, Moore JP, Matthews TJ, Langedijk JP, Meloen RH, Boersma WJ, Claassen E. A hidden region in the third variable domain of HIV-1 IIIB gp120 identified by a monoclonal antibody. AIDS Res Hum Retroviruses. 1993 Jul;9(7):605–612. [PubMed]
  • Lange JM, Karam M, Piot P. Boost for vaginal microbicides against HIV. Lancet. 1993 Nov 27;342(8883):1356–1356. [PubMed]
  • Layne SP, Merges MJ, Spouge JL, Dembo M, Nara PL. Blocking of human immunodeficiency virus infection depends on cell density and viral stock age. J Virol. 1991 Jun;65(6):3293–3300. [PMC free article] [PubMed]
  • Leeder JS, Dosch HM, Harper PA, Lam P, Spielberg SP. Fluorescence-based viability assay for studies of reactive drug intermediates. Anal Biochem. 1989 Mar;177(2):364–372. [PubMed]
  • Leer RJ, van Luijk N, Posno M, Pouwels PH. Structural and functional analysis of two cryptic plasmids from Lactobacillus pentosus MD353 and Lactobacillus plantarum ATCC 8014. Mol Gen Genet. 1992 Aug;234(2):265–274. [PubMed]
  • Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996 Aug 9;86(3):367–377. [PubMed]
  • Marcon L, Choe H, Martin KA, Farzan M, Ponath PD, Wu L, Newman W, Gerard N, Gerard C, Sodroski J. Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. J Virol. 1997 Mar;71(3):2522–2527. [PMC free article] [PubMed]
  • Matsushita S, Robert-Guroff M, Rusche J, Koito A, Hattori T, Hoshino H, Javaherian K, Takatsuki K, Putney S. Characterization of a human immunodeficiency virus neutralizing monoclonal antibody and mapping of the neutralizing epitope. J Virol. 1988 Jun;62(6):2107–2114. [PMC free article] [PubMed]
  • McGroarty JA. Probiotic use of lactobacilli in the human female urogenital tract. FEMS Immunol Med Microbiol. 1993 Apr;6(4):251–264. [PubMed]
  • Merson MH. Slowing the spread of HIV: agenda for the 1990s. Science. 1993 May 28;260(5112):1266–1268. [PubMed]
  • Moore JP. HIV vaccines. Back to primary school. Nature. 1995 Jul 13;376(6536):115–115. [PubMed]
  • Moore JP. Coreceptors: implications for HIV pathogenesis and therapy. Science. 1997 Apr 4;276(5309):51–52. [PubMed]
  • Moore JP, Cao Y, Qing L, Sattentau QJ, Pyati J, Koduri R, Robinson J, Barbas CF, 3rd, Burton DR, Ho DD. Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120. J Virol. 1995 Jan;69(1):101–109. [PMC free article] [PubMed]
  • Moore JP, Sattentau QJ, Wyatt R, Sodroski J. Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies. J Virol. 1994 Jan;68(1):469–484. [PMC free article] [PubMed]
  • Nara PL, Fischinger PJ. Quantitative infectivity assay for HIV-1 and-2. Nature. 1988 Mar 31;332(6163):469–470. [PubMed]
  • Pauwels R, De Clercq E. Development of vaginal microbicides for the prevention of heterosexual transmission of HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Mar 1;11(3):211–221. [PubMed]
  • Paxton WA, Dragic T, Koup RA, Moore JP. The beta-chemokines, HIV type 1 second receptors, and exposed uninfected persons. AIDS Res Hum Retroviruses. 1996 Sep 1;12(13):1203–1207. [PubMed]
  • Roben P, Moore JP, Thali M, Sodroski J, Barbas CF, 3rd, Burton DR. Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1. J Virol. 1994 Aug;68(8):4821–4828. [PMC free article] [PubMed]
  • Rosenberg MJ, Holmes KK. Virucides in prevention of HIV infection. Research Priorities. World Health Organization Working Group on Virucides. Sex Transm Dis. 1993 Jan-Feb;20(1):41–44. [PubMed]
  • Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996 Aug 22;382(6593):722–725. [PubMed]
  • Sattentau QJ, Moore JP. The role of CD4 in HIV binding and entry. Philos Trans R Soc Lond B Biol Sci. 1993 Oct 29;342(1299):59–66. [PubMed]
  • Soto-Ramirez LE, Renjifo B, McLane MF, Marlink R, O'Hara C, Sutthent R, Wasi C, Vithayasai P, Vithayasai V, Apichartpiyakul C, et al. HIV-1 Langerhans' cell tropism associated with heterosexual transmission of HIV. Science. 1996 Mar 1;271(5253):1291–1293. [PubMed]
  • Sullivan N, Sun Y, Li J, Hofmann W, Sodroski J. Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates. J Virol. 1995 Jul;69(7):4413–4422. [PMC free article] [PubMed]
  • von Brunn A, Brand M, Reichhuber C, Morys-Wortmann C, Deinhardt F, Schödel F. Principal neutralizing domain of HIV-1 is highly immunogenic when expressed on the surface of hepatitis B core particles. Vaccine. 1993;11(8):817–824. [PubMed]
  • Weislow OS, Kiser R, Fine DL, Bader J, Shoemaker RH, Boyd MR. New soluble-formazan assay for HIV-1 cytopathic effects: application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J Natl Cancer Inst. 1989 Apr 19;81(8):577–586. [PubMed]
  • Weiss RA, Clapham PR. Hot fusion of HIV. Nature. 1996 Jun 20;381(6584):647–648. [PubMed]
  • White-Scharf ME, Potts BJ, Smith LM, Sokolowski KA, Rusche JR, Silver S. Broadly neutralizing monoclonal antibodies to the V3 region of HIV-1 can be elicited by peptide immunization. Virology. 1993 Jan;192(1):197–206. [PubMed]
  • Zhang L, Huang Y, He T, Cao Y, Ho DD. HIV-1 subtype and second-receptor use. Nature. 1996 Oct 31;383(6603):768–768. [PubMed]

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