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Targeting the rhesus macaque TRIM5α gene to enhance the susceptibility of CD4+ T cells to HIV-1 infection

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Abstract

The host range of human immunodeficiency virus type 1 (HIV-1) is extremely narrow, which has hampered the establishment of non-human primate models for HIV-1 infection. The species-specific innate immune factor tripartite motif 5 alpha (TRIM5α) is a key molecule that confers potent resistance against HIV-1 infection. In this study, we targeted the TRIM5α gene of rhesus macaques (rhTRIM5α) using the transcription activator-like effector nuclease (TALEN) to study the effect on HIV-1 infection. CD4+ T cells were separated from the peripheral blood of rhesus macaques by magnetic cell sorting, and the positive rate was greater than 99%. TALEN plasmids targeting rhTRIM5α were constructed and introduced into CD4+ T cells by electroporation, with a transfection efficiency of approximately 25%. The genome of the targeted cells was extracted, and the target efficiency was analyzed by T7E1 enzyme digestion. After sorting the positive transductants, the TALENs induced rhTRIM5α mutations at a rate of more than 40%. The ability of the HIV-1 virus to infect the targeted cells was demonstrated by ELISA. The results showed that targeting rhTRIM5α enhanced the susceptibility to HIV-1 infection. This finding will pave the way for further establishment of a new rhesus macaque model for HIV-1 studies.

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Acknowledgements

This study was supported by the Ministry of Science and Technology of China (2013ZX10001-004-002-005) and the Natural Science Foundation of Hubei Provincial Department of Education (Q20162110).

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Authors and Affiliations

  1. College of Life Science and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing, 100124, People’s Republic of China

    Xiaoli Wang, Yahong Yuan & Yi Zeng

  2. Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Renmin Road 32, Shiyan, 442000, Hubei, People’s Republic of China

    Xiaoli Wang, Qing Yu, Yahong Yuan & Dongsheng Li

  3. Institute of Virology, Chinese Academy of Preventive Medicine, Beijing, People’s Republic of China

    Zhiping Teng

Authors
  1. Xiaoli Wang
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  2. Qing Yu
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  3. Yahong Yuan
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  4. Zhiping Teng
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  5. Dongsheng Li
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  6. Yi Zeng
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Correspondence to Dongsheng Li or Yi Zeng.

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Wang, X., Yu, Q., Yuan, Y. et al. Targeting the rhesus macaque TRIM5α gene to enhance the susceptibility of CD4+ T cells to HIV-1 infection. Arch Virol 162, 793–798 (2017). https://doi.org/10.1007/s00705-016-3169-0

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  • DOI: https://doi.org/10.1007/s00705-016-3169-0

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