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 b-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 HIV-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 b 1,3-glucan but not by b 1,6-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.

A killer mimotope with therapeutic activity against AIDS-related opportunistic microorganisms inhibits ex vivo HIV-1 replication / Casoli, Claudio; Pilotti, E.; Perno, C. F.; Balestra, E.; Polverini, Eugenia; Cassone, A.; Conti, Stefania; Magliani, Valter; Polonelli, Luciano. - In: AIDS. - ISSN 0269-9370. - 20:7(2006), pp. 975-980. [10.1097/01.aids.0000222068.14878.0d]

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

CASOLI, Claudio;POLVERINI, Eugenia;CONTI, Stefania;MAGLIANI, Valter;POLONELLI, Luciano
2006-01-01

Abstract

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 b-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 HIV-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 b 1,3-glucan but not by b 1,6-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.
2006
A killer mimotope with therapeutic activity against AIDS-related opportunistic microorganisms inhibits ex vivo HIV-1 replication / Casoli, Claudio; Pilotti, E.; Perno, C. F.; Balestra, E.; Polverini, Eugenia; Cassone, A.; Conti, Stefania; Magliani, Valter; Polonelli, Luciano. - In: AIDS. - ISSN 0269-9370. - 20:7(2006), pp. 975-980. [10.1097/01.aids.0000222068.14878.0d]
File in questo prodotto:
File Dimensione Formato  
Abstract_AIDS2006.pdf

non disponibili

Tipologia: Abstract
Licenza: Creative commons
Dimensione 177.55 kB
Formato Adobe PDF
177.55 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Polverini_2006AIDS.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 3.19 MB
Formato Adobe PDF
3.19 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1494224
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 23
social impact