title: Targeting the rhesus macaque TRIM5α gene to enhance the susceptibility of CD4+T cells to HIV-1 infection.
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.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing, 100124, People's Republic of China.|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.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing, 100124, People's Republic of China.|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.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Virology, Chinese Academy of Preventive Medicine, Beijing, People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Teng
authors.affiliation: 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. dsli1698@126.com.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, 100 Ping Le Yuan, Chaoyang District, Beijing, 100124, People's Republic of China. zengy@public.bta.net.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D018390:Gene Targeting; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009154:Mutation
chemical_list: D002352:Carrier Proteins