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- W295547198 abstract "G-quadruplexes are non-canonical nucleic acid structures: their presence and functional role have been established in telomeres, oncogene promoters and coding regions of the human chromosome. In particular, they act as silencers in the promoter regions of human genes and putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Moreover, they have been proposed to be directly involved in gene regulation at the level of transcription. We investigated G-quadruplex formation in the HIV-1 proviral genome to assess the potential for viral inhibition through G-quadruplex stabilization. Here we show that the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional regulation with striking similarities to eukaryotic promoters and that treatment with a G-quadruplex ligand inhibits HIV-1 infectivity. In addition, we found three conserved putative G-quadruplex forming sequences uniquely clustered in the coding region for the accessory protein Nef that were efficiently stabilized or induced by G-quadruplex ligands. Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was significantly repressed in an antiviral assay. Finally, a comprehensive screening of G-quadruplex ligands against HIV-1 disclosed significant potential of some of them as HIV-1 inhibitors, likely with a G-quadruplex-mediated mechanism of action. These findings open up the possibility of inhibiting the HIV-1 by G-quadruplex-interacting small molecules, providing a new pathway to the development of anti-HIV-1 drugs with unprecedented mechanism of action." @default.
- W295547198 created "2016-06-24" @default.
- W295547198 creator A5024171817 @default.
- W295547198 date "2014-01-01" @default.
- W295547198 modified "2023-09-27" @default.
- W295547198 title "G-QUADRUPLEXES IN THE HIV-1 GENOME AS ANTIVIRAL TARGETS" @default.
- W295547198 hasPublicationYear "2014" @default.
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