Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. 1997 Nov; 41(11): 2394–2398.
PMCID: PMC164134

Novel antimicrobial peptides derived from human immunodeficiency virus type 1 and other lentivirus transmembrane proteins.


We have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the natural antimicrobial peptides cecropins and magainins in overall structure but bear no sequence homology to them or other members of their class. We describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides (LLPs). The results of this study demonstrate that they are potent and selective antibacterial peptides: the prototype sequence, LLP1, is bactericidal to both gram-positive and gram-negative organisms at micromolar concentrations in 10 mM phosphate buffer. Furthermore, LLP1 kills bacteria quite rapidly, causing a 1,000-fold reduction in viable organisms within 50 s. Peptides corresponding to sequences from three lentivirus envelope proteins were synthesized and characterized. Several of these peptides are selective, killing bacteria at concentrations 50- to 100-fold lower than those required to lyse erythrocytes. Development of antimicrobial agents based on these peptides may lead to improved therapeutics for the management of a variety of infectious diseases.

Full Text

The Full Text of this article is available as a PDF (167K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Agerberth B, Lee JY, Bergman T, Carlquist M, Boman HG, Mutt V, Jörnvall H. Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur J Biochem. 1991 Dec 18;202(3):849–854. [PubMed]
  • Baker MA, Maloy WL, Zasloff M, Jacob LS. Anticancer efficacy of Magainin2 and analogue peptides. Cancer Res. 1993 Jul 1;53(13):3052–3057. [PubMed]
  • Boman HG. Peptide antibiotics and their role in innate immunity. Annu Rev Immunol. 1995;13:61–92. [PubMed]
  • Casteels P, Ampe C, Jacobs F, Vaeck M, Tempst P. Apidaecins: antibacterial peptides from honeybees. EMBO J. 1989 Aug;8(8):2387–2391. [PMC free article] [PubMed]
  • Chernomordik L, Chanturiya AN, Suss-Toby E, Nora E, Zimmerberg J. An amphipathic peptide from the C-terminal region of the human immunodeficiency virus envelope glycoprotein causes pore formation in membranes. J Virol. 1994 Nov;68(11):7115–7123. [PMC free article] [PubMed]
  • Chou PY, Fasman GD. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. [PubMed]
  • Cox JA, Comte M, Fitton JE, DeGrado WF. The interaction of calmodulin with amphiphilic peptides. J Biol Chem. 1985 Feb 25;260(4):2527–2534. [PubMed]
  • Diamond G, Zasloff M, Eck H, Brasseur M, Maloy WL, Bevins CL. Tracheal antimicrobial peptide, a cysteine-rich peptide from mammalian tracheal mucosa: peptide isolation and cloning of a cDNA. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3952–3956. [PMC free article] [PubMed]
  • Eisenberg D, Schwarz E, Komaromy M, Wall R. Analysis of membrane and surface protein sequences with the hydrophobic moment plot. J Mol Biol. 1984 Oct 15;179(1):125–142. [PubMed]
  • Eisenberg D, Wesson M. The most highly amphiphilic alpha-helices include two amino acid segments in human immunodeficiency virus glycoprotein 41. Biopolymers. 1990 Jan;29(1):171–177. [PubMed]
  • Fontenot JD, Ball JM, Miller MA, David CM, Montelaro RC. A survey of potential problems and quality control in peptide synthesis by the fluorenylmethoxycarbonyl procedure. Pept Res. 1991 Jan-Feb;4(1):19–25. [PubMed]
  • Fujii G, Horvath S, Woodward S, Eiserling F, Eisenberg D. A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41. Protein Sci. 1992 Nov;1(11):1454–1464. [PMC free article] [PubMed]
  • Gawrisch K, Han KH, Yang JS, Bergelson LD, Ferretti JA. Interaction of peptide fragment 828-848 of the envelope glycoprotein of human immunodeficiency virus type I with lipid bilayers. Biochemistry. 1993 Mar 30;32(12):3112–3118. [PubMed]
  • Habermann E. Bee and wasp venoms. Science. 1972 Jul 28;177(4046):314–322. [PubMed]
  • Hancock RE. Peptide antibiotics. Lancet. 1997 Feb 8;349(9049):418–422. [PubMed]
  • Hill CP, Yee J, Selsted ME, Eisenberg D. Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991 Mar 22;251(5000):1481–1485. [PubMed]
  • Kaiser ET, Kézdy FJ. Peptides with affinity for membranes. Annu Rev Biophys Biophys Chem. 1987;16:561–581. [PubMed]
  • Kelley KJ. Using host defenses to fight infectious diseases. Nat Biotechnol. 1996 May;14(5):587–590. [PubMed]
  • Lee JY, Boman A, Sun CX, Andersson M, Jörnvall H, Mutt V, Boman HG. Antibacterial peptides from pig intestine: isolation of a mammalian cecropin. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9159–9162. [PMC free article] [PubMed]
  • Lehrer RI, Selsted ME, Szklarek D, Fleischmann J. Antibacterial activity of microbicidal cationic proteins 1 and 2, natural peptide antibiotics of rabbit lung macrophages. Infect Immun. 1983 Oct;42(1):10–14. [PMC free article] [PubMed]
  • Miller MA, Cloyd MW, Liebmann J, Rinaldo CR, Jr, Islam KR, Wang SZ, Mietzner TA, Montelaro RC. Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein. Virology. 1993 Sep;196(1):89–100. [PubMed]
  • Miller MA, Garry RF, Jaynes JM, Montelaro RC. A structural correlation between lentivirus transmembrane proteins and natural cytolytic peptides. AIDS Res Hum Retroviruses. 1991 Jun;7(6):511–519. [PubMed]
  • Miller MA, Mietzner TA, Cloyd MW, Robey WG, Montelaro RC. Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein. AIDS Res Hum Retroviruses. 1993 Nov;9(11):1057–1066. [PubMed]
  • Moore AJ, Devine DA, Bibby MC. Preliminary experimental anticancer activity of cecropins. Pept Res. 1994 Sep-Oct;7(5):265–269. [PubMed]
  • Nicolas P, Mor A. Peptides as weapons against microorganisms in the chemical defense system of vertebrates. Annu Rev Microbiol. 1995;49:277–304. [PubMed]
  • Pearson RD, Steigbigel RT, Davis HT, Chapman SW. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. [PMC free article] [PubMed]
  • Rushlow K, Olsen K, Stiegler G, Payne SL, Montelaro RC, Issel CJ. Lentivirus genomic organization: the complete nucleotide sequence of the env gene region of equine infectious anemia virus. Virology. 1986 Dec;155(2):309–321. [PubMed]
  • Sarin VK, Kent SB, Tam JP, Merrifield RB. Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. Anal Biochem. 1981 Oct;117(1):147–157. [PubMed]
  • Schonwetter BS, Stolzenberg ED, Zasloff MA. Epithelial antibiotics induced at sites of inflammation. Science. 1995 Mar 17;267(5204):1645–1648. [PubMed]
  • Selsted ME, Brown DM, DeLange RJ, Lehrer RI. Primary structures of MCP-1 and MCP-2, natural peptide antibiotics of rabbit lung macrophages. J Biol Chem. 1983 Dec 10;258(23):14485–14489. [PubMed]
  • Srinivas SK, Srinivas RV, Anantharamaiah GM, Segrest JP, Compans RW. Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein. J Biol Chem. 1992 Apr 5;267(10):7121–7127. [PubMed]
  • Steiner H, Hultmark D, Engström A, Bennich H, Boman HG. Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature. 1981 Jul 16;292(5820):246–248. [PubMed]
  • Tencza SB, Mietzner TA, Montelaro RC. Calmodulin-binding function of LLP segments from the HIV type 1 transmembrane protein is conserved among natural sequence variants. AIDS Res Hum Retroviruses. 1997 Feb 10;13(3):263–269. [PubMed]
  • Tencza SB, Miller MA, Islam K, Mietzner TA, Montelaro RC. Effect of amino acid substitutions on calmodulin binding and cytolytic properties of the LLP-1 peptide segment of human immunodeficiency virus type 1 transmembrane protein. J Virol. 1995 Aug;69(8):5199–5202. [PMC free article] [PubMed]
  • van Hofsten P, Faye I, Kockum K, Lee JY, Xanthopoulos KG, Boman IA, Boman HG, Engström A, Andreu D, Merrifield RB. Molecular cloning, cDNA sequencing, and chemical synthesis of cecropin B from Hyalophora cecropia. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2240–2243. [PMC free article] [PubMed]
  • Yuan T, Mietzner TA, Montelaro RC, Vogel HJ. Characterization of the calmodulin binding domain of SIV transmembrane glycoprotein by NMR and CD spectroscopy. Biochemistry. 1995 Aug 22;34(33):10690–10696. [PubMed]
  • Zasloff M. Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5449–5453. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...