Display options
Cite
Deng J, Qu X, Lu P, et al. Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1. Mol Ther Nucleic Acids. 2017;6:233-242doi: 10.1016/j.omtn.2017.01.002.
Deng, J., Qu, X., Lu, P., Yang, X., Zhu, Y., Ji, H., Wang, Y., Jiang, Z., Li, X., Zhong, Y., Yang, H., Pan, H., Young, W. B., & Zhu, H. (2017). Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1. Molecular therapy. Nucleic acids, 6233-242. https://doi.org/10.1016/j.omtn.2017.01.002
Deng, Junxiao, et al. "Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1." Molecular therapy. Nucleic acids vol. 6 (2017): 233-242. doi: https://doi.org/10.1016/j.omtn.2017.01.002
Deng J, Qu X, Lu P, Yang X, Zhu Y, Ji H, Wang Y, Jiang Z, Li X, Zhong Y, Yang H, Pan H, Young WB, Zhu H. Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1. Mol Ther Nucleic Acids. 2017 Mar 17;6:233-242. doi: 10.1016/j.omtn.2017.01.002. Epub 2017 Jan 24. PMID: 28325289; PMCID: PMC5363508.
Copy Download .nbib Format: NLM
Share it on

Mol Ther Nucleic Acids. 2017 Mar 17;6:233-242. doi: 10.1016/j.omtn.2017.01.002. Epub 2017 Jan 24.

Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1.

Molecular therapy. Nucleic acids

Junxiao Deng, Xiying Qu, Panpan Lu, Xinyi Yang, Yuqi Zhu, Haiyan Ji, Yanan Wang, Zhengtao Jiang, Xian Li, Yangcheng Zhong, He Yang, Hanyu Pan, Won-Bin Young, Huanzhang Zhu

Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.
  2. Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
  3. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: [email protected].

PMID: 28325289 PMCID: PMC5363508 DOI: 10.1016/j.omtn.2017.01.002

Abstract

HIV-1 inserts its proviral DNA into the infected host cells, by which HIV proviral DNA can then be duplicated along with each cell division. Thus, provirus cannot be eradicated completely by current antiretroviral therapy. We have developed an innovative strategy to silence the HIV provirus by targeted DNA methylation on the HIV promoter region. We genetically engineered a chimeric DNA methyltransferase 1 composed of designed zinc-finger proteins to become ZF2 DNMT1. After transient transfection of the molecular clone encoding this chimeric protein into HIV-1 infected or latently infected cells, efficient suppression of HIV-1 expression by the methylation of CpG islands in 5'-LTR was observed and quantified. The effective suppression of HIV in latently infected cells by ZF2-DNMT1 is stable and can last through about 40 cell passages. Cytotoxic caused by ZF2-DNMT1 was only observed during cellular proliferation. Taken together, our results demonstrate the potential of this novel approach for anti-HIV-1 therapy.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: DNMT1; HIV-1; chimeric protein; gene therapy; methylation; zinc finger

References

  1. EMBO J. 1990 Apr;9(4):1157-64 - PubMed
  2. Nat Rev Genet. 2009 Nov;10(11):805-11 - PubMed
  3. Antiviral Res. 2013 Dec;100(3):688-97 - PubMed
  4. J Virol. 2012 Dec;86(23):13081-4 - PubMed
  5. Gene Ther. 2014 May;21(5):490-5 - PubMed
  6. Biol Psychiatry. 2010 Sep 1;68(5):408-15 - PubMed
  7. PLoS Pathog. 2009 Aug;5(8):e1000554 - PubMed
  8. Nature. 2010 Jan 14;463(7278):237-40 - PubMed
  9. Trends Genet. 1997 Aug;13(8):335-40 - PubMed
  10. PLoS One. 2012;7(1):e30687 - PubMed
  11. Trends Biochem Sci. 2014 Jul;39(7):310-8 - PubMed
  12. Virology. 2015 Dec;486:228-38 - PubMed
  13. J Virol. 2006 Mar;80(6):2873-83 - PubMed
  14. Hum Vaccin Immunother. 2013 May;9(5):993-1001 - PubMed
  15. Science. 2011 May 13;332(6031):786 - PubMed
  16. PLoS Genet. 2012 Jun;8(6):e1002750 - PubMed
  17. Nucleic Acids Res. 2007;35(1):100-12 - PubMed
  18. J Virol. 2015 Oct;89(20):10176-89 - PubMed
  19. J Virol. 2005 Jan;79(2):876-83 - PubMed
  20. PLoS Pathog. 2009 Jun;5(6):e1000495 - PubMed
  21. Epigenetics. 2012 Apr;7(4):350-60 - PubMed
  22. Nature. 2007 May 24;447(7143):425-32 - PubMed
  23. PLoS One. 2014 Jan 29;9(1):e87703 - PubMed
  24. Oncogene. 2015 Oct;34(43):5427-35 - PubMed
  25. AIDS. 2005 Jul 1;19(10):1081-9 - PubMed
  26. Cell. 2013 Oct 24;155(3):519-29 - PubMed
  27. Nat Rev Drug Discov. 2003 Aug;2(8):624-34 - PubMed
  28. Curr Top Microbiol Immunol. 2006;310:211-50 - PubMed
  29. Nature. 2012 Jul 25;487(7408):439-40 - PubMed
  30. Sci Rep. 2016 Apr 12;6:24100 - PubMed
  31. PLoS Pathog. 2014 Nov 13;10(10):e1004473 - PubMed
  32. Exp Mol Pathol. 2010 Dec;89(3):291-300 - PubMed
  33. Retrovirology. 2006 Oct 12;3:69 - PubMed
  34. Antiviral Res. 2013 Jun;98(3):394-400 - PubMed
  35. Mol Cell Biol. 2002 Apr;22(7):2124-35 - PubMed
  36. Nucleic Acids Res. 2013 Sep;41(16):7771-82 - PubMed
  37. Retrovirology. 2012 Jan 16;9:6 - PubMed
  38. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1615-20 - PubMed
  39. Nucleic Acids Res. 2006 Feb 25;34(4):1182-8 - PubMed
  40. Mol Cell Biol. 2011 Dec;31(23):4720-34 - PubMed
  41. Science. 2012 Mar 16;335(6074):1291 - PubMed
  42. J Virol. 2013 Nov;87(22):12110-20 - PubMed
  43. Mol Ther. 2016 Mar;24(3):508-21 - PubMed
  44. Nature. 2015 Apr 9;520(7546):243-7 - PubMed
  45. J Acquir Immune Defic Syndr (1988). 1993 Jun;6(6):541-9 - PubMed
  46. Philos Trans R Soc Lond B Biol Sci. 2013 Jan 5;368(1609):20110336 - PubMed
  47. Biochem Biophys Res Commun. 1990 Apr 16;168(1):141-7 - PubMed
  48. Cell. 2013 May 9;153(4):773-84 - PubMed
  49. Nat Rev Genet. 2012 May 29;13(7):484-92 - PubMed
  50. Viruses. 2013 Feb 21;5(2):753-7 - PubMed
  51. J Virol. 2013 Jun;87(11):6521-5 - PubMed
  52. Nucleic Acids Res. 2016 Jul 8;44(12):5615-28 - PubMed
  53. DNA Res. 2009 Aug;16(4):195-211 - PubMed
  54. J Virol. 2009 Aug;83(16):8289-92 - PubMed
  55. J Virol. 2003 Apr;77(7):4025-32 - PubMed
  56. PLoS One. 2013;8(1):e54801 - PubMed
  57. Nature. 2015 Jan 15;517(7534):321-6 - PubMed
  58. BMC Bioinformatics. 2010 May 06;11:230 - PubMed

Publication Types

Grant support