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The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1

  1. Author:
    Giomarelli, B.
    Provvedi, R.
    Meacci, F.
    Maggi, T.
    Medaglini, D.
    Pozzi, G.
    Mori, T.
    McMahon, J. B.
    Gardella, R.
    Boyd, M. R.

  2. Author Address

    Univ Siena, LAMMB, Dept Biol Mol, Policlin Scotte, 1S Viale Bracci, I-53100 Siena, Italy Univ Siena, LAMMB, Dept Biol Mol, Policlin Scotte, I-53100 Siena, Italy Natl Canc Inst, Mol Targets Drug Discovery Program, NCI Ctr Canc Res, Frederick, MD USA NCI, Sci Applicat Int Corp, Frederick, MD USA Pozzi G Univ Siena, LAMMB, Dept Biol Mol, Policlin Scotte, 1S Viale Bracci, I-53100 Siena, Italy
    1. Year: 2002
  2. Journal: Aids
    1. 16
    2. 10
    3. Pages: 1351-1356
  4. Type of Article: Article
  1. Abstract:

    Objective: To explore the feasibility of expressing the potent HIV-inactivating protein, cyanovirin-N (CV-N), in the human commensal bacterium Streptococcus gordonii, as a possible approach for local delivery of CV-N to prevent sexual transmission of HIV-1. Design and methods: To express CV-N in S. gordonii, we used the host-vector system we had previously developed. CV-N was expressed as a fusion protein both attached to the bacterial surface and secreted in soluble form in the supernatant of liquid cultures. The soluble form of recombinant CV-N was tested for gp120-binding activity in an enzyme-linked immunosorbent assay, whereas S. gordonii strain expressing CV-N on the surface was analyzed in an in vitro HIV capturing assay. Results: Two recombinant S. gordonii strains secreting or displaying CV-N on the bacterial surface were constructed and the expression of CV-N was confirmed by immunoblot and flow- cytometric analysis. The secreted form of recombinant CV-N exhibited a concentration-dependent binding to the envelope glycoprotein gp120 of HIV-1, whereas CV-N displayed on the bacterial surface was able to capture HIV virions efficiently. Conclusion: The anti-HIV protein CV-N in S. gordonii was expressed in a biologically active form. This represents a first step in the development of a system to deliver and maintain an effective concentration of a microbicide in the vaginal mucosa. (C) 2002 Lippincott Williams Wilkins.

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