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Journal of Virology, December 2001, p. 11408-11416, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11408-11416.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

NF-kappa B cis-Acting Motifs of the Human Immunodeficiency Virus (HIV) Long Terminal Repeat Regulate HIV Transcription in Human Macrophages

Susana Asin,1 Gary D. Bren,1 Eva M. Carmona,1 Nancie J. Solan,1 and Carlos V. Paya1,2,3,*

Department of Immunology1 and Divisions of Infectious Diseases2 and Experimental Pathology,3 Mayo Clinic, Rochester, Minnesota 55905

Received 29 January 2001/Accepted 3 August 2001

The role of NF-kappa B in the reactivation of human immunodeficiency virus (HIV) from latency in CD4 T lymphocytes is well documented. However, its role in driving HIV transcription in human macrophages, which contain a constitutive nuclear pool of NF-kappa B, is less well understood. In this study we have investigated the role that the constitutive pool of NF-kappa B and the NF-kappa B cis-acting motifs of the HIV long terminal repeat (LTR) play in regulating HIV transcription in human monocytic cells and primary macrophages. Inhibition of the constitutive nuclear pool of NF-kappa B (RelA and RelB) in the promonocytic U937 cell line using dominant-negative Ikappa Balpha significantly decreases HIV replication. Moreover, it is demonstrated that in the differentiated monocytic cell line THP1, which contains a constitutive nuclear pool of NF-kappa B (RelB),an HIV provirus containing mutations of the kappa B cis-acting sites in the LTR is transcriptionally impaired. Reduction of the constitutive pool of NF-kappa B in human macrophages by an adenovirus vector expressing a dominant-negative Ikappa Balpha also reduces HIV transcription. Lastly, mutation of the NF-kappa B cis-acting sites in the LTR of an R5 HIV provirus completely abrogates the first cycle of HIV transcription. These studies indicate that the cis-acting NF-kappa B motifs of the HIV LTR are critical in initiating HIV transcription in human macrophages and suggest that the constitutive nuclear pool of NF-kappa B is important in regulating HIV transcription in these cells.

* Corresponding author. Mailing address: Mayo Clinic, 200 First St., SW, Guggenheim 501, Rochester, MN 55905. Phone: (507) 284-3747. Fax: (507) 284-3757. E-mail: paya{at}mayo.edu.

Journal of Virology, December 2001, p. 11408-11416, Vol. 75, No. 23
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.23.11408-11416.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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