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Journal of Virology, May 2000, p. 4658-4665, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Activation of Transcription Factors NF-kappa B and NF-IL-6 by Human Immunodeficiency Virus Type 1 Protein R (Vpr) Induces Interleukin-8 Expression

Philippe Roux,1,2 Caroline Alfieri,1,2 Mohammed Hrimech,2 Eric A. Cohen,2 and Jerome E. Tanner3,*

Laboratory of Molecular Virology, Ste-Justine Hospital Research Center,1 and Department of Microbiology and Immunology, Université de Montréal,2 Montréal, Québec H3T 1C5, and Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa Medical School, Ottawa, Ontario K1H 8L1,3 Canada

Received 13 July 1999/Accepted 21 February 2000

Human immunodeficiency virus (HIV)-positive individuals express elevated levels of interleukin-8 (IL-8), which is believed to be responsible for some of the clinical manifestations occurring during AIDS. We report here that virion-derived HIV type 1 (HIV-1) protein R (Vpr) increased IL-8 expression in primary T cells and macrophages, as well as in the T-cell line Jurkat, the monocytic cell line U937, and the epithelial cell line A549. Vpr appeared to increase IL-8 expression and IL-8 promoter activity by activating transcription factors NF-kappa B and NF-IL-6. Elevated Vpr was also shown to increase transcription of the NF-kappa B and NF-IL-6 enhancer-containing viral promoters for HIV, cytomegalovirus, and simian virus 40, as well as increase the expression of IL-6 and IL-10 in primary macrophages and in A549 cells, tumor necrosis factor alpha expression in primary T cells, and IL-6 and gamma interferon expression in U937 cells. These results suggest a new role for Vpr in the pathogenesis of HIV infection, namely, the activation of transcription factors NF-IL-6 and NF-kappa B.

* Corresponding author. Mailing address: Molecular Genetics Research, Rm. R306, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Rd., Ottawa, Ontario K1H 8L1, Canada. Phone: (613) 738-3926. Fax: (450) 424-8293. E-mail: jtanner{at}mgcheo.med.uottawa.ca.

Journal of Virology, May 2000, p. 4658-4665, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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