Targeting the rhesus macaque TRIM5α gene to enhance the susceptibility of CD4+ T cells to HIV-1 infection
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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.
KeywordsAcquire Immune Deficiency Syndrome Spry Domain TALEN Target Acquire Immune Deficiency Syndrome Vaccine Acquire Immune Deficiency Syndrome Treatment
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).
Compliance with ethical standards
The authors declare that they have no competing interests.
Ethical standard statement and informed consent
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