1887

Abstract

Antimicrobial peptides are effectors of innate immunity, providing their hosts with rapid non-specific defence against parasitic invaders. In this report, the effects are assessed of two well-characterized antimicrobial amphipathic peptides (melittin and cecropin) on human immunodeficiency virus 1 (HIV-1) replication and gene expression in acutely infected cells at subtoxic concentrations. Production of infectious, cell-free virus was inhibited in a dose-dependent manner, with ID values in the range 0·9–1·5 μM for melittin and 2–3 μM for cecropin. Analysis of the effect of melittin on cell-associated virus production revealed decreased levels of Gag antigen and HIV-1 mRNAs. Transient transfection assays with HIV long terminal repeat (LTR)-driven reporter gene plasmids indicated that melittin has a direct suppressive effect on activity of the HIV LTR. HIV LTR activity was also reduced in human cells stably transfected with retroviral expression plasmids for the melittin or cecropin gene. It is concluded that antimicrobial peptides such as melittin and cecropin are capable of inhibiting cell-associated production of HIV-1 by suppressing HIV-1 gene expression.

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1998-04-01
2024-03-29
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References

  1. Agawa Y., Lee S., Ono S., Aoyagi H., Ohno M., Taniguchi T., Anzai K., Kirino Y. 1991; Interaction with phospholipid bilayers, ion channel formation, and antimicrobial activity of basic amphipathic alpha-helical model peptides of various chain lengths. Journal of Biological Chemistry 266:20218–20222
    [Google Scholar]
  2. Ahmad I., Perkins W. R., Lupan D. M., Selsted M. E., Janoff A. S. 1995; Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with in vivo anti-fungal activity. Biochimica et Biophysica Acta 1237:109–114
    [Google Scholar]
  3. Ammentorp B. 1994 Antiretrovirale Wirkung von Melittin bei der Rauscher-Leukämie-Infektion in vivo und in vitro PhD thesis Ludwig-Maximilian’s University of Munich, Germany:
    [Google Scholar]
  4. Andreu D., Upbach J., Boman A., Wahlin B., Wade D., Merrifield R. B., Boman H. G. 1992; Shortened cecropin A-melittin hybrids. FEBS Letters 296:190–194
    [Google Scholar]
  5. Baghian A., Jaynes J., Enright F., Kousolas K. G. 1997; An amphipathic alpha-helical synthetic peptide analogue of melittin inhibits herpes simplex virus-1 (HSV-1)-induced cell fusion and virus spread. Peptides 18:177–183
    [Google Scholar]
  6. Bazzo R., Tappin M. J., Pastore A., Harvey T. S., Carver J. A., Campbell I. D. 1988; The structure of melittin. A 1H-NMR study in methanol. European Journal of Biochemistry 173:139–146
    [Google Scholar]
  7. Bevins C. L., Zasloff M. 1990; Peptides from frog skin. Annual Review of Biochemistry 59:395–414
    [Google Scholar]
  8. Boman H. G. 1995; Peptide antibiotics and their role in innate immunity. Annual Review of Immunology 13:61–92
    [Google Scholar]
  9. Boman H. G., Agerberth B., Boman A. 1993; Mechanisms of action on Escherichia coli of cecropine P1 and PR-39, two antibacterial peptides from pig intestine. Infection and Immunity 61:2978–2984
    [Google Scholar]
  10. Brack-Werner R., Kleinschmidt A., Ludvigsen A., Mellert W., Neumann M., Herrmann R., Khim M. C. L., Burny A., Müller-Lantzsch N., Stavrou D., Erfle V. 1992; Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines. AIDS (Philadelphia) 6:273–285
    [Google Scholar]
  11. Chesebro B., Buller R., Portis J., Wehrly K. 1990; Failure ofhuman immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. Journal of Virology 64:215–221
    [Google Scholar]
  12. Chretien S., Dubart A., Beaupain D., Raich N., Grandchamp B., Rosa J., Gossens M. 1988; Alternative transcription and splicing of the human porphobilinogendeaminase gene result in either tissue-specific or in housekeeping expression. Proceedings of the National Academy of Sciences, USA 85:5–10
    [Google Scholar]
  13. Christensen B., Fink J., Merrifield R. B., Mauzerall D. 1988; Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes. Proceedings of the National Academy of Sciences, USA 85:5072–5076
    [Google Scholar]
  14. Clark M. A., Conway T. M., Shorr R. G. L., Crooke S. T. 1987; Identification and isolation of a mammalian protein which is antigenically and functionally related to the phospholipase A2 stimulatory peptide melittin. Journal of Biological Chemistry 262:4402–4406
    [Google Scholar]
  15. Crabtree G. 1989; Contingent genetic regulatory events in T lymphocyte activation. Science 243:355–361
    [Google Scholar]
  16. Esser A. F., Bartholomew R. M., Jensen F. C., Müller-Eberhardt H. J. 1979; Disassembly of viral membranes by complement independent channel formation. Proceedings of the National Academy of Sciences, USA 76:5843–5847
    [Google Scholar]
  17. Fearon D. T., Locksley R. M. 1996; The instructive role of innate immunity in the acquired immune response. Science 272:50–54
    [Google Scholar]
  18. Fisher P. J., Prendergast F. G., Ehrhardt M. R., Urbauer J. L., Wand A. J., Sedarous S. S., McCormick D. J., Buckley P. J. 1994; Calmodulin interacts with amphiphilic peptides composed of all d-amino acids. Nature 368:651–653
    [Google Scholar]
  19. Frankel A. D., Pabo C. O. 1988; Cellular uptake of the Tat protein from human immunodeficiency virus. Cell 55:1189–1193
    [Google Scholar]
  20. Gaynor R. 1992; Cellular transcription factors involved in the regulation of HIV-1 gene expression. AIDS (Philadelphia) 6:347–363
    [Google Scholar]
  21. Gravitt K. R., Ward N. E., O’Brian C. A. 1994; Inhibition of protein kinase C by melittin: antagonism of binding interactions between melittin and the catalytic domain by active-site binding of MgATP. Biochemical Pharmacology 47:425–427
    [Google Scholar]
  22. Habermann E., Jentsch J. 1967; Sequence analysis of melittin from tryptic and peptic degradation products. Hoppe-Seyler’s Zeitschrift fuer Physiologische Chemie 348:37–50
    [Google Scholar]
  23. Hancock R. E. W. 1997; Peptide antibiotics. Lancet 349:418–422
    [Google Scholar]
  24. Hill C. S., Treisman R. 1995; Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80:199–211
    [Google Scholar]
  25. Hoover T., Mikovits J., Court D., Liu Y. L., Raziuddin Kung H. F. 1996; A nuclear matrix-specific factor that binds a specific segment of the negative regulatory element (NRE) of HIV-1 LTR and inhibits NF-kappa B activity. Nucleic Acids Research 24:1895–1900
    [Google Scholar]
  26. Hornsby P., Yang L., Lala D., Cheng C. Y., Salmons B. 1992; A modified procedure for replica plating of mammalian cells allowing selection of clones based on gene expression. BioTechniques 12:244–251
    [Google Scholar]
  27. Lidholm D.-A., Gudmundsson G. H., Xanthopoulos K. G., Boman H. G. 1987; Insect immunity: cDNA clones coding for the precursor forms of cecropins A and D, antibacterial proteins from Hyalophora cecropia . FEBS Letters 226:8–12
    [Google Scholar]
  28. Ludvigsen A., Werner T., Gimbel W., Erfle V., Brack-Werner R. 1996; Down-modulation of HIV-1 LTR activity by an extra-LTR nef gene fragment. Virology 216:245–251
    [Google Scholar]
  29. McCune J. M. 1995; Viral latency in HIV disease. Cell 82:183–188
    [Google Scholar]
  30. Mackewicz C. E., Blackbourn D. J., Levy J. A. 1995; CD8+ T cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proceedings of the National Academy of Sciences, USA 92:2308–2312
    [Google Scholar]
  31. Makropoulos V., Bruning T., Schulzeosthoff K. 1996; Selenium-mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity. Archives of Toxicology 70:277–283
    [Google Scholar]
  32. Mann D. L., O’Brien S. J., Gilbert D. A., Reid Y., Popovic M., Read-Connole E., Gallo R. C., Gazdar A. F. 1989; Origin of the HIV-susceptible human CD4+ cell line H9. AIDS Research and Human Retroviruses 5:253–255
    [Google Scholar]
  33. Marcos J. F., Beachy R. N., Houghten R. A., Blondelle S. E., Perez-Paya E. 1995; Inhibition of plant virus infection by melittin. Proceedings of the National Academy of Sciences, USA 92:12466–12469
    [Google Scholar]
  34. Mellert W., Kleinschmidt A., Schmidt J., Festl H., Emler S., Roth W. K., Erfle V. 1990; Infection of human fibroblasts and osteoblastlike cells with HIV-1. AIDS (Philadelphia) 4:527–535
    [Google Scholar]
  35. Mosmann T. 1983; Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65:55–63
    [Google Scholar]
  36. Neumann M., Harrison J., Saltarelli M., Hadziyannis E., Erfle V., Felber B. K., Pavlakis G. N. 1994; Splicing variability in HIV type 1 revealed by quantitative polymerase chain reaction. AIDS Research and Human Retroviruses 10:1531–1542
    [Google Scholar]
  37. Parada L. F., Tabin C. J., Shih C., Weinberg R. A. 1982; Human EJ bladder carcinoma oncogene is a homologue of Harvey sarcoma virus ras gene. Nature 297:474–478
    [Google Scholar]
  38. Pomerantz R. J., Bagasra O., Baltimore D. 1992; Cellular latency of human immunodeficiency virus type 1. Current Opinions in Immunology 4:475–480
    [Google Scholar]
  39. Popovic M., Read-Connole B., Gallo R. C. 1984a; T4 positive human neoplastic cell lines susceptible to and permissive for HTLV-III. Lancet ii:1472–1473
    [Google Scholar]
  40. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. 1984b; Detection, isolation and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224:497–500
    [Google Scholar]
  41. Price J., Turner D., Cepko C. 1987; Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. Proceedings of the National Academy of Sciences, USA 84:156–160
    [Google Scholar]
  42. Rauer M. 1994 Nachweis und Quantifizierung des Felinen Immundefizienz-Virus in natürlich infizierten Katzen mit Hilfe der Polymerase-Kettenreaktion PhD thesis Ludwig-Maximilian’s University of Munich, Germany:
    [Google Scholar]
  43. Reitz M. S., Guo H.-G., Oleske J., Hoxie J., Popovic M., Read-Connole E., Markham P., Streicher H., Gallo R. C. 1992; On the historical origins of HIV-1 (MN) and (RF). AIDS Research and Human Retroviruses 8:1539–1541
    [Google Scholar]
  44. Saller R. 1994 Design von locus-und gewebespezifischen Vektoren für eine in vivo Gentherapie PhD thesis Ludwig-Maximilian’s University of Munich, Germany:
    [Google Scholar]
  45. Saltarelli M. J., Hadziyannis E., Hart C. E., Harrison J. V., Felber B. K., Spira T. J., Pavlakis G. N. 1996; Analysis of human immunodeficiency virus type 1 mRNA splicing patterns during disease progression in peripheral blood mononuclear cells from infected individuals. AIDS Research and Human Retroviruses 12:1443–1456
    [Google Scholar]
  46. Sharma S. V. 1993; Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells. Oncogene 8:939–947
    [Google Scholar]
  47. Smith G. L. 1996; Virus proteins that bind cytokines, chemokines or interferons. Current Opinions in Immunology 8:467–471
    [Google Scholar]
  48. Sparer T. E., Tripp R. A., Dillehay D. L., Hermiston T. W., Wold W. S. M., Gooding L. R. 1996; The role of human adenovirus early region 3 proteins (gp19K, 10·4K, 14·5K and 14·7K) in a murine pneumonia model. Journal of Virology 70:2431–2439
    [Google Scholar]
  49. Steiner H., Hultmark D., Engstrom A., Bennich H., Boman H. G. 1981; Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248
    [Google Scholar]
  50. Stoiber H., Pinter C., Siccardi A. G., Clivio A., Dierich M. P. 1996; Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55). Journal of Experimental Medicine 183:307–310
    [Google Scholar]
  51. Terwilliger T. C., Eisenberg D. 1982; The structure of melittin. II. Interpretation of the structure. Journal of Biological Chemistry 257:6016–6022
    [Google Scholar]
  52. Tissot C., Mechti N. 1995; Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. Journal of Biological Chemistry 270:14891–14898
    [Google Scholar]
  53. Vlasak R., Unger-Ullmann C., Kreil G. 1983; Nucleotide sequence of cloned cDNA coding for honeybee prepromelittin. European Journal of Biochemistry 135:123–126
    [Google Scholar]
  54. Wachinger M., Saermark T., Erfle V. 1992; Influence of amphipathic peptides on the HIV-1 production in persistently infected T-lymphoma cells. FEBS Letters 309:235–241
    [Google Scholar]
  55. Wade D., Andreu D., Mitchell S. A., Silveira A. M. V., Boman A., Boman H. G., Merrifield R. B. 1992; Antibacterial peptides designed as analogs or hybrids of cecropins and melittin. International Journal of Peptide Protein Research 40:429–436
    [Google Scholar]
  56. Wintersperger S., Salmons B., Miethke T., Erfle V., Wagner H., Günzburg W. H. 1995; Negative-acting factor and superantigen are separable activities of the mouse mammary tumor virus long terminal repeat. Proceedings of the National Academy of Sciences, USA 92:2745–2749
    [Google Scholar]
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