Inhibition of HIV-1 replication by cell-penetrating peptides binding Rev.
New therapeutic agents able to block HIV-1 replication are eagerly sought after to increase the possibilities of treatment of resistant viral strains. In this report, we describe a rational strategy to identify small peptide sequences owning the dual property of penetrating within lymphocytes and of binding to a protein target. Such sequences were identified for two important HIV-1 regulatory proteins, Tat and Rev. Their association to a stabilizing domain consisting of human small ubiquitin-related modifier-1 (SUMO-1) allowed the generation of small proteins named SUMO-1 heptapeptide protein transduction domain for binding Tat (SHPT) and SUMO-1 heptapeptide protein transduction domain for binding Rev (SHPR), which are stable and efficiently penetrate within primary lymphocytes. Analysis of the antiviral activity of these proteins showed that one SHPR is active in both primary lymphocytes and macrophages, whereas one SHPT is active only in the latter cells. These proteins may represent prototypes of new therapeutic agents targeting the crucial functions exerted by both viral regulatory factors.
Roisin
Armelle
A
Laboratoire de Biologie Moléculaire de la Cellule, UMR5161, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Robin
Jean-Philippe
JP
Dereuddre-Bosquet
Nathalie
N
Vitte
Anne-Laure
AL
Dormont
Dominique
D
Clayette
Pascal
P
Jalinot
Pierre
P
D019380:Anti-HIV Agents / Q000494:pharmacology; D015694:Gene Products, rev / Q000187:drug effects* / Q000378:metabolism; D015696:Gene Products, tat / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015694:Gene Products, rev; D015696:Gene Products, tat; D010446:Peptide Fragments; D025842:SUMO-1 Protein; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus