A killer mimotope with therapeutic activity against AIDS-related opportunistic micro-organisms inhibits ex-vivo HIV-1 replication

Claudio Casoli, Elisabetta Pilotti, Carlo Federico Perno, Emanuela Balestra, Eugenia Polverini, Antonio Cassone, Stefania Conti, Walter Magliani, Luciano Polonelli

Research output: Contribution to journalArticle

Abstract

Objective: To verify whether a synthetic therapeutic killer decapeptide (KP), a functional mimotope of a yeast killer toxin with wide-spectrum microbicidal activity, inclusive of AIDS-related opportunistic micro-organisms, through interaction with β-glucan receptors, which has been found to possess sequence homology with critical segments in gp160 V1/V2 and V3 loops, may also be inhibiting HIV-1 replication. Methods: Primary peripheral blood mononuclear cells (PBMCs) cultures established from H1V-1-infected patients were treated with KP in comparison with zidovudine and supernatants and cells were harvested for analysis of HIV RNA and proviral contents, respectively. Virus production in exogenous in-vitro PBMCs infection with lymphocytotropic and monocytotropic HIV-1 strains was also assessed in presence of KP by enzyme-linked immunosorbent assay HIV p24 gag antigen detection. The binding affinity of KP to CD4, CCR5 and CXCR4 was evaluated on CD4-CCR5 or CD4-CXCR4 transfected astroglioma cell lines. Results: KP was shown to be devoid of cytotoxicity on PBMCs and to inhibit HIV-1 replication in PBMCs of a patient in the acute phase of infection. The antiretroviral activity of KP, which proved to be more potent than zidovudine at micromolar concentrations, is abolished by β 1,3-glucan but not by β1,6-glucan. Down-regulation of CCR5 co-receptor, and/or physical block of the gp120-receptor interaction are possible mechanisms of KP activity. Conclusion: KP appears to be the first antibody-derived short peptide displaying an inhibitory activity against HIV-1 and related opportunistic micro-organisms by different mechanisms of action.

Original languageEnglish
Pages (from-to)975-980
Number of pages6
JournalAIDS (London, England)
Volume20
Issue number7
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Antibodies
  • Antiretroviral therapy
  • Opportunistic infections
  • Receptor
  • Virus-cell interaction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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