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

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 beta-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 beta 1,3-glucan but not by beta 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.

• Authors: Claudio Casoli, Elisabetta Pilotti, Carlo Federico Perno, Emanuela Balestra, Eugenia Polverini, Antonio Cassone, Stefania Conti, Walter Magliani, Luciano Polonelli
• Journal: AIDS (London, England) (AIDS) Vol. 20 Issue 7 Pg. 975-80 (Apr 24 2006) ISSN: 0269-9370 [Print] England
• PMID: 16603848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• HIV Envelope Protein gp160
• Peptides
• RNA, Viral
• Receptors, CCR5
• Receptors, CXCR4
• Zidovudine

Topics

• AIDS-Related Opportunistic Infections (drug therapy, immunology, virology)
• Anti-HIV Agents (immunology, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Down-Regulation (immunology)
• HIV Envelope Protein gp160 (chemistry)
• HIV Infections (drug therapy, immunology, virology)
• HIV-1 (drug effects, physiology)
• Humans
• Leukocytes, Mononuclear (immunology)
• Molecular Mimicry (immunology)
• Peptides (chemistry, immunology, therapeutic use)
• RNA, Viral (analysis)
• Receptors, CCR5 (immunology)
• Receptors, CXCR4 (immunology)
• Sequence Alignment
• Virus Replication (drug effects, immunology)
• Zidovudine (immunology, therapeutic use)