Inhibition of HIV-1 replication by cell-penetrating peptides binding rev

Autor: Jean-Philippe Robin, Dominique Dormont, Nathalie Dereuddre-Bosquet, Armelle Roisin, Pierre Jalinot, Pascal Clayette, Anne-Laure Vitte
Přispěvatelé: Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Ministère de la Défense, École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Université Paris-Sud - Paris 11 (UP11), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE)
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Journal of Biological Chemistry
Journal of Biological Chemistry, 2004, 279 (10), pp.9208-9214. ⟨10.1074/jbc.M311594200⟩
Journal of Biological Chemistry 10 (279), 9208-9214. (2004)
Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2004, 279 (10), pp.9208-9214. ⟨10.1074/jbc.M311594200⟩
ISSN: 0021-9258
1083-351X
DOI: 10.1074/jbc.M311594200⟩
Popis: International audience; 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.
Databáze: OpenAIRE