PMID- 32961937 OWN - NLM STAT- MEDLINE DCOM- 20210302 LR - 20210310 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 12 IP - 9 DP - 2020 Sep 18 TI - CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR. LID - 10.3390/v12091040 [doi] LID - 1040 AB - The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the human immunodeficiency virus (HIV)-1 LTR promoter. Here, we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting polycomb group (PcG/PRC) corepressor complexes or polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs corepressor complexes enhancing the recruitment of RNA polymerase II (RNAP II) at HIV LTR. Knockdown of certain components of PRC1 and PRC2 also led to the reactivation of latent proviruses. Similarly, the treatment of latently infected primary CD4+ T cells with the PRC2/EZH2 inhibitor, 3-deazaneplanocin A (DZNep), led to their reactivation. FAU - Sharma, Adhikarimayum Lakhikumar AU - Sharma AL AUID- ORCID: 0000-0002-9969-8642 AD - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. FAU - Hokello, Joseph AU - Hokello J AUID- ORCID: 0000-0002-6721-5933 AD - Department of Basic Science, Faculty of Science and Technology, Kampala International University-Western Campus, P.O. Box 71, Bushenyi, Uganda. FAU - Sonti, Shilpa AU - Sonti S AD - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. FAU - Zicari, Sonia AU - Zicari S AUID- ORCID: 0000-0003-1240-8057 AD - Section of Intercellular Interactions, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. AD - Department of Pediatric Medicine, The Bambino Gesu Children's Hospital, 00165 Rome, Italy. FAU - Sun, Lin AU - Sun L AD - Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC 20037, USA. FAU - Alqatawni, Aseel AU - Alqatawni A AD - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. FAU - Bukrinsky, Michael AU - Bukrinsky M AUID- ORCID: 0000-0002-8593-0770 AD - Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA. FAU - Simon, Gary AU - Simon G AD - Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC 20037, USA. FAU - Chauhan, Ashok AU - Chauhan A AD - Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA. FAU - Daniel, Rene AU - Daniel R AD - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. FAU - Tyagi, Mudit AU - Tyagi M AUID- ORCID: 0000-0003-1493-8051 AD - Center for Translational Medicine, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. AD - Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC 20037, USA. LA - eng GR - R01 DA041746/DA/NIDA NIH HHS/United States GR - R03 DA033900/DA/NIDA NIH HHS/United States GR - R21 DA033924/DA/NIDA NIH HHS/United States GR - National Institute on Drug Abuse (NIDA), NIH Grants, 7R01DA041746-02, 5R21DA033924-02, 5R03DA033900-02 to MT/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200918 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Cell Cycle Proteins) RN - 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein) RN - 0 (PRC1 protein, human) RN - 0 (RBPJ protein, human) RN - 0 (RNA, Small Interfering) RN - EC 2.7.7.- (RNA Polymerase II) SB - IM MH - Cell Cycle Proteins/genetics/metabolism MH - Cell Line MH - Chromatin Immunoprecipitation MH - Epigenomics MH - Gene Expression Regulation, Viral MH - Gene Knockdown Techniques MH - HIV Infections/virology MH - HIV Long Terminal Repeat MH - HIV-1/genetics/*physiology MH - Humans MH - Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics/*metabolism MH - Promoter Regions, Genetic MH - Proviruses/genetics MH - RNA Polymerase II/metabolism MH - RNA, Small Interfering MH - Transcriptome MH - Virus Activation MH - Virus Latency/genetics/*physiology PMC - PMC7551090 OTO - NOTNLM OT - CBF-1 OT - HIV-1 OT - PRC1 OT - PRC2 OT - chromatin OT - epigenetics OT - latency OT - transcription COIS- The authors declare no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. EDAT- 2020/09/24 06:00 MHDA- 2021/03/03 06:00 PMCR- 2020/09/01 CRDT- 2020/09/23 01:02 PHST- 2020/08/14 00:00 [received] PHST- 2020/09/09 00:00 [revised] PHST- 2020/09/16 00:00 [accepted] PHST- 2020/09/23 01:02 [entrez] PHST- 2020/09/24 06:00 [pubmed] PHST- 2021/03/03 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - v12091040 [pii] AID - viruses-12-01040 [pii] AID - 10.3390/v12091040 [doi] PST - epublish SO - Viruses. 2020 Sep 18;12(9):1040. doi: 10.3390/v12091040.