title: Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5'-LTR promoter.
abstract: HIV-1 latency remains the primary obstacle to the eradication of this virus. The current latency-reversing agents cannot effectively and specifically eliminate latent HIV-1 reservoirs. Therefore, better approaches are urgently needed. In this study, we describe a novel strategy to reactivate latent HIV-1 using zinc-finger transcription factors composed of designer zinc-finger proteins and the transcriptional activation domain VP64. For the first time, we demonstrate that ZF-VP64 with HIV-1 long terminal repeat (LTR) promoter-specific affinity could significantly reactivate HIV-1 expression from latently infected cells without altering cell proliferation or cell cycle progression. We also provide evidence that the reactivation of HIV-1 by ZF-VP64 occurs through specific binding to the 5'-LTR promoter. Our results demonstrate the potential of this novel approach for anti-HIV-1 latency therapy.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Qu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, MA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors