1. Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles.
- Author
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Peretti S, Schiavoni I, Pugliese K, and Federico M
- Subjects
- Adult, Blotting, Western, CD4 Antigens metabolism, Cell Line, Flow Cytometry, Genes, Reporter, Green Fluorescent Proteins analysis, HIV-1 physiology, Humans, Male, Proteins analysis, Receptors, CCR5 metabolism, Receptors, CXCR4 metabolism, Recombinant Fusion Proteins, Thymidine Kinase genetics, Viral Proteins genetics, nef Gene Products, Human Immunodeficiency Virus, Anti-HIV Agents pharmacology, Cell Death, Ganciclovir pharmacology, Gene Products, nef genetics, HIV-1 drug effects, Receptors, HIV metabolism, Virosomes pharmacology
- Abstract
We recently showed that both replicating and resting cells cultivated with ganciclovir (GCV) were killed when challenged with vesicular stomatitis virus G glycoprotein pseudotyped HIV-1-based virus-like particles (VLPs) carrying the Nef7 (i.e., an HIV-1 Nef mutant incorporating in virions at high levels)/herpes simplex virus-1 thymidine kinase (HSV-TK) fusion product. On this basis, a novel anti-HIV therapeutic approach based on Nef7/TK VLPs expressing X4 or R5 HIV cell receptor complexes has been attempted. We here report that (CD4-CXCR4) and (CD4-CCR5) Nef7-based VLPs efficiently enter cells infected by X4- or R5-tropic HIV-1 strains, respectively. Importantly, the delivery of the VLP-associated Nef7/TK led to cell death upon GCV treatment. Of interest, VLPs were effective also against non-replicating, HIV-1-infected primary human monocyte-derived macrophages. HIV-targeted VLPs represent a promising candidate for the treatment of persistently HIV-1-infected cells that are part of virus reservoirs resistant to HAART therapies.
- Published
- 2006
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