Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1
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 targe...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225311730121X |
| _version_ | 1818379910869155840 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Junxiao Deng |
| collection | DOAJ |
| description | 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. Keywords: HIV-1, methylation, zinc finger, chimeric protein, DNMT1, gene therapy |
| first_indexed | 2024-12-14T02:10:18Z |
| format | Article |
| id | doaj.art-8d195c47f1424fe5b8be022e7106d31b |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-14T02:10:18Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-8d195c47f1424fe5b8be022e7106d31b2022-12-21T23:20:47ZengElsevierMolecular Therapy: Nucleic Acids2162-25312017-03-016233242Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1Junxiao Deng0Xiying Qu1Panpan Lu2Xinyi Yang3Yuqi Zhu4Haiyan Ji5Yanan Wang6Zhengtao Jiang7Xian Li8Yangcheng Zhong9He Yang10Hanyu Pan11Won-Bin Young12Huanzhang Zhu13State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaDepartment of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USAState Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China; Corresponding author: Huanzhang Zhu, State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, China.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. Keywords: HIV-1, methylation, zinc finger, chimeric protein, DNMT1, gene therapyhttp://www.sciencedirect.com/science/article/pii/S216225311730121X |
| spellingShingle | 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 Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 Molecular Therapy: Nucleic Acids |
| title | Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 |
| title_full | Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 |
| title_fullStr | Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 |
| title_full_unstemmed | Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 |
| title_short | Specific and Stable Suppression of HIV Provirus Expression In Vitro by Chimeric Zinc Finger DNA Methyltransferase 1 |
| title_sort | specific and stable suppression of hiv provirus expression in vitro by chimeric zinc finger dna methyltransferase 1 |
| url | http://www.sciencedirect.com/science/article/pii/S216225311730121X |
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