PMID- 16611917 OWN - NLM STAT- MEDLINE DCOM- 20060522 LR - 20211020 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 80 IP - 9 DP - 2006 May TI - Hexamethylbisacetamide remodels the human immunodeficiency virus type 1 (HIV-1) promoter and induces Tat-independent HIV-1 expression but blunts cell activation. PG - 4570-9 AB - Hexamethylbisacetamide (HMBA) induces human immunodeficiency virus type 1 (HIV-1) gene expression in latently infected T-cell and monocytoid cell lines. We find that HMBA activation of viral expression is Tat independent but, like Tat, increases the efficiency of elongation of the HIV-1 promoter (long terminal repeat [LTR]) transcripts. Further, exposure to HMBA induces chromatin remodeling at nucleosome 1 (Nuc-1) near the start site of LTR transcription but does so without increasing histone acetylation or altering histone methylation near Nuc-1. Of note, despite enhanced proviral expression, HMBA suppressed HIV infection ex vivo in primary blood mononuclear cell (PBMC) cultures. Treatment with HMBA did not alter expression of the HIV coreceptors, CCR5 and CXCR4, in PBMCs but down-regulated CD4. Finally, HMBA interferes with cell proliferation and activation; it suppressed expression of Ki67 and CD25 and in PBMCs exposed to mitogen. As HMBA has been tested in oncology trials, its unusual properties make it a useful reagent for future studies of HIV promoter regulation and a novel prototype molecule for therapeutics that abort the latent proviral state of chronic HIV infection. FAU - Klichko, Vladimir AU - Klichko V AD - North Texas Veterans Health Care Systems, Dallas, Texas 75216, USA. FAU - Archin, Nancy AU - Archin N FAU - Kaur, Rupinderjeet AU - Kaur R FAU - Lehrman, Ginger AU - Lehrman G FAU - Margolis, David AU - Margolis D LA - eng GR - R01 AI045297/AI/NIAID NIH HHS/United States GR - R01 AI-45297/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Acetamides) RN - 0 (Biomarkers) RN - 0 (CD4 Antigens) RN - 0 (Gene Products, tat) RN - 0 (Histones) RN - 0 (Ki-67 Antigen) RN - 0 (Receptors, Interleukin-2) RN - 0 (Receptors, Virus) RN - 0 (tat Gene Products, Human Immunodeficiency Virus) RN - EC 3.1.- (Endodeoxyribonucleases) RN - EC 3.1.22.1 (deoxyribonuclease II) SB - IM MH - Acetamides/*pharmacology MH - Biomarkers MH - CD4 Antigens/metabolism MH - CD4-Positive T-Lymphocytes/*drug effects/immunology/metabolism MH - Cells, Cultured MH - Chromatin Assembly and Disassembly/drug effects MH - Endodeoxyribonucleases/metabolism MH - Gene Expression Regulation, Viral/*drug effects/genetics MH - Gene Products, tat/metabolism MH - HIV Long Terminal Repeat/genetics MH - HIV-1/*drug effects/*genetics/physiology MH - Histones/genetics MH - Humans MH - Ki-67 Antigen/metabolism MH - Promoter Regions, Genetic/*genetics MH - Receptors, Interleukin-2/metabolism MH - Receptors, Virus/metabolism MH - Transcription, Genetic/drug effects/genetics MH - tat Gene Products, Human Immunodeficiency Virus PMC - PMC1472000 EDAT- 2006/04/14 09:00 MHDA- 2006/05/23 09:00 PMCR- 2006/09/01 CRDT- 2006/04/14 09:00 PHST- 2006/04/14 09:00 [pubmed] PHST- 2006/05/23 09:00 [medline] PHST- 2006/04/14 09:00 [entrez] PHST- 2006/09/01 00:00 [pmc-release] AID - 80/9/4570 [pii] AID - 2161-05 [pii] AID - 10.1128/JVI.80.9.4570-4579.2006 [doi] PST - ppublish SO - J Virol. 2006 May;80(9):4570-9. doi: 10.1128/JVI.80.9.4570-4579.2006.