Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles

Journal Article · Sun Feb 05 04:00:00 EST 2006 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2005.0· OSTI ID:20779455

Peretti, Silvia ^[1]; Schiavoni, Ilaria ^[1]; Pugliese, Katherina ^[1]; Federico, Maurizio ^[1]

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1. AIDS Center, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome (Italy)

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.

• OSTI ID: 20779455
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 345; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AIDS VIRUS
APOPTOSIS
GLYCOPROTEINS
HERPES SIMPLEX
MACROPHAGES
MONOCYTES
MUTANTS
RECEPTORS
THERAPY
THYMIDINE