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DOI	10.1073/pnas.2105927118
	Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth
	Salinas T.R.W.; Zhang Y.; Sarnello D.; Zhyvoloup A.; Marchand L.R.; Fert A.; Planas D.; Lodha M.; Chatterjee D.; Karwacz K.; Oxenford S.; Routy J.-P.; Irlbeck D.; Amrine-Madsen H.; Ancuta P.; Fassati A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:48
英文摘要	Among CD4+ T cells, T helper 17 (Th17) cells are particularly susceptible to HIV-1 infection and are depleted from mucosal sites, which causes damage to the gut barrier, resulting in a microbial translocation-induced systemic inflammation, a hallmark of disease progression. Furthermore, a proportion of latently infected Th17 cells persist long term in the gastrointestinal lymphatic tract where a low-level HIV-1 transcription is observed. This residual viremia contributes to chronic immune activation. Thus, Th17 cells are key players in HIV pathogenesis and viral persistence. It is, however, unclear why these cells are highly susceptible to HIV-1 infection. Th17 cell differentiation depends on the expression of the master transcriptional regulator RORC2, a retinoic acid-related nuclear hormone receptor that regulates specific transcriptional programs by binding to promoter/enhancer DNA. Here, we report that RORC2 is a key host cofactor for HIV replication in Th17 cells. We found that specific inhibitors that bind to the RORC2 ligand-binding domain reduced HIV replication in CD4+ T cells. The depletion of RORC2 inhibited HIV-1 infection, whereas its overexpression enhanced it. RORC2 was also found to promote HIV-1 gene expression by binding to the nuclear receptor responsive element in the HIV-1 long terminal repeats (LTR). In treated HIV-1 patients, RORC2+ CD4 T cells contained more proviral DNA than RORC22 cells. Pharmacological inhibition of RORC2 potently reduced HIV-1 outgrowth in CD4+ T cells from antiretroviral-treated patients. Altogether, these results provide an explanation as to why Th17 cells are highly susceptible to HIV-1 infection and suggest that RORC2 may be a cell-specific target for HIV-1 therapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Gene expression; HIV-1; Hormone receptor; RORC2; Th17
语种	英语
scopus关键词	hormone receptor; retinoic acid; transcription factor; transcription factor RORC2; unclassified drug; cytokine; retinoid related orphan receptor gamma; RORC protein, human; transcription factor; adult; aged; Article; CD4+ T lymphocyte; cell differentiation; clinical article; female; gene expression; human; human cell; Human immunodeficiency virus 1; Human immunodeficiency virus 1 infection; long terminal repeat; male; nonhuman; Th17 cell; virus replication; gene expression; gene expression regulation; genetics; growth, development and aging; Human immunodeficiency virus 1; Human immunodeficiency virus infection; immunology; lymphocyte activation; metabolism; middle aged; physiology; primary cell culture; regulatory T lymphocyte; T lymphocyte subpopulation; Th17 cell; viremia; virology; Adult; CD4-Positive T-Lymphocytes; Cell Differentiation; Cytokines; Female; Gene Expression; Gene Expression Regulation, Viral; HIV Infections; HIV-1; Humans; Lymphocyte Activation; Male; Middle Aged; Nuclear Receptor Subfamily 1, Group F, Member 3; Primary Cell Culture; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Th17 Cells; Transcription Factors; Viremia; Virus Replication
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/250962
作者单位	Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montréal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Institute of Immunity and Transplantation, University College London, London, NW3 2QG, United Kingdom; Translational Research Office-Medicinal Chemistry, University College London, School of Pharmacy, London, WC1N 1AX, United Kingdom; Division of Hematology and Chronic Viral Illness Service, McGill University Medical Centre, Montréal, QC H4A 3J1, Canada; ViiV Healthcare, Research Triangle Park, NC 27709-3398, United States; Division of Infection and Immunity, University College London, London, WC1E 6JF, United Kingdom
推荐引用方式 GB/T 7714	Salinas T.R.W.,Zhang Y.,Sarnello D.,et al. Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth[J],2021,118(48).
APA	Salinas T.R.W..,Zhang Y..,Sarnello D..,Zhyvoloup A..,Marchand L.R..,...&Fassati A..(2021).Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth.Proceedings of the National Academy of Sciences of the United States of America,118(48).
MLA	Salinas T.R.W.,et al."Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth".Proceedings of the National Academy of Sciences of the United States of America 118.48(2021).