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Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5′-LTR promoter

Gene Therapy volume 21, pages 490–495 (2014)Cite this article

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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.

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Acknowledgements

We thank the NIH AIDS Research and Reference Reagent Program for providing the J-Lat clone A10.6 cells. We also thank Prof Jianqing Xu (Shanghai Medical College of Fudan University) for providing the pNL4-3-EGFP plasmid. This work was supported by the National Grand Program on Key Infectious Disease (2014ZX10001003) and National Natural Science Foundation of China (31271418 to H Zhu).

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Authors and Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China

    P Wang, X Qu, X Wang, X Zhu, H Zeng & H Zhu

  2. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, MA, USA

    H Chen

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Correspondence to H Zhu.

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Wang, P., Qu, X., Wang, X. et al. Specific reactivation of latent HIV-1 with designer zinc-finger transcription factors targeting the HIV-1 5′-LTR promoter. Gene Ther 21, 490–495 (2014). https://doi.org/10.1038/gt.2014.21

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