Selective elimination of HIV-1-infected cells by Env-directed, HIV-1-based virus-like particles.
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.
Peretti
Silvia
S
AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Schiavoni
Ilaria
I
Pugliese
Katherina
K
Federico
Maurizio
M
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D005434:Flow Cytometry; D015774:Ganciclovir / Q000494:pharmacology*; D015693:Gene Products, nef / Q000235:genetics*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D011506:Proteins / Q000032:analysis; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D013937:Thymidine Kinase / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D022701:Virosomes / Q000494:pharmacology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D015693:Gene Products, nef; D011506:Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D022701:Virosomes; D054311:nef Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir