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Journal of Virology, May 2006, p. 4570-4579, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4570-4579.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Hexamethylbisacetamide Remodels the Human Immunodeficiency Virus Type 1 (HIV-1) Promoter and Induces Tat-Independent HIV-1 Expression but Blunts Cell Activation

Vladimir Klichko,1,2 Nancy Archin,3 Rupinderjeet Kaur,2 Ginger Lehrman,2 and David Margolis3*

North Texas Veterans Health Care Systems, Dallas, Texas 75216,1 University of Texas Southwestern Medical Center at Dallas, Texas 75390,2 University of North Carolina at Chapel Hill, North Carolina 27599-74353

Received 14 October 2005/ Accepted 9 February 2006

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.

* Corresponding author. Mailing address: University of North Carolina at Chapel Hill, 3302 Michael Hooker Research Ctr., CB#7435, Chapel Hill, NC 27599-7435. Phone: (919) 966-6388. Fax: (919) 966-0584. E-mail: dmargo{at}med.unc.edu.

Journal of Virology, May 2006, p. 4570-4579, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4570-4579.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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