气候变化领域集成服务门户(CCPortal): HIV proviral DNA integration can drive T cell growth ex vivo

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DOI	10.1073/PNAS.2013194117
	HIV proviral DNA integration can drive T cell growth ex vivo
	Yoon J.K.; Holloway J.R.; Wells D.W.; Kaku M.; Jetton D.; Brown R.; Coffin J.M.
发表日期	2021
ISSN	00278424
起始页码	32880
结束页码	32882
卷号	117 期号:52
英文摘要	In vivo clonal expansion of HIV-infected T cells is an important mechanism of viral persistence. In some cases, clonal expansion is driven by HIV proviral DNA integrated into one of a handful of genes. To investigate this phenomenon in vitro, we infected primary CD4+ T cells with an HIV construct expressing GFP and, after nearly 2 mo of culture and multiple rounds of activation, analyzed the resulting integration site distribution. In each of three replicates from each of two donors, we detected large clusters of integration sites with multiple breakpoints, implying clonal selection. These clusters all mapped to a narrow region within the STAT3 gene. The presence of hybrid transcripts splicing HIV to STAT3 sequences supports a model of LTR-driven STAT3 overexpression as a driver of preferential growth. Thus, HIV integration patterns linked to selective T cell outgrowth can be reproduced in cell culture. The single report of an HIV provirus in a case of AIDS-associated B-cell lymphoma with an HIV provirus in the same part of STAT3 also has implications for HIV-induced malignancy. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	AIDS lymphoma; HIV persistence; STAT3
语种	英语
scopus关键词	STAT3 protein; STAT3 protein, human; virus DNA; cell culture; cell proliferation; clonal evolution; genetics; human; Human immunodeficiency virus; physiology; provirus; T lymphocyte; virology; virus DNA cell DNA interaction; Cell Proliferation; Cells, Cultured; Clonal Evolution; DNA, Viral; HIV; Humans; Proviruses; STAT3 Transcription Factor; T-Lymphocytes; Virus Integration
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179641
作者单位	Program in Immunology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, United States; Program in Pharmacology and Experimental Therapeutics, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, United States; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21704, United States; Program in Genetics, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, United States; Department of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111, United States; Department of Preclinical Research and Development, AVROBIO, Inc., Cambridge, MA 02139, United States; Department of Biological and Chemical Sciences, New York Institute of Technology, Old Westbury, NY 11568, United States
推荐引用方式 GB/T 7714	Yoon J.K.,Holloway J.R.,Wells D.W.,et al. HIV proviral DNA integration can drive T cell growth ex vivo[J],2021,117(52).
APA	Yoon J.K..,Holloway J.R..,Wells D.W..,Kaku M..,Jetton D..,...&Coffin J.M..(2021).HIV proviral DNA integration can drive T cell growth ex vivo.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Yoon J.K.,et al."HIV proviral DNA integration can drive T cell growth ex vivo".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).