@article{fbca3a8a52224407b3719665cbac9de8,
title = "CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR",
abstract = "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.",
keywords = "CBF-1, Chromatin, Epigenetics, HIV-1, Latency, PRC1, PRC2, Transcription",
author = "Sharma, {Adhikarimayum Lakhikumar} and Joseph Hokello and Shilpa Sonti and Sonia Zicari and Lin Sun and Aseel Alqatawni and Michael Bukrinsky and Gary Simon and Ashok Chauhan and Rene Daniel and Mudit Tyagi",
note = "Funding Information: Funding: The work performed in the laboratories of the authors was partially funded by National Institute on Drug Abuse (NIDA), NIH Grants, 7R01DA041746-02, 5R21DA033924-02, 5R03DA033900-02 to M.T. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Center for Research Resources or the US National Institutes of Health. Funding Information: The work performed in the laboratories of the authors was partially funded by National Institute on Drug Abuse (NIDA), NIH Grants, 7R01DA041746-02, 5R21DA033924-02, 5R03DA033900-02 to M.T. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Center for Research Resources or the US National Institutes of Health. We thank the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, US National Institutes of Health; M. Gately (Hoffmann La Roche) for human recombinant interleukin 2; We are also thankful to the Flow Cytometry core facility of George Washington University. Moreover, we would also like to thank the Center for Translational Medicine, Thomas Jefferson University including all staff members for technical support and assistance for the experiment of this study. Publisher Copyright: {\textcopyright} 2020 by the authors.",
year = "2020",
month = sep,
doi = "10.3390/v12091040",
language = "English",
volume = "12",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",
}