Previous Article | Next Article ![]()
J Virol, July 1998, p. 5862-5869, Vol. 72, No. 7
Program in Virology and Immunology,
University of Massachusetts Medical Center, Worcester, Massachusetts
016051;
Department of Microbiology,
Boston University School of Medicine, Boston, Massachusetts
021182; and
Institute of Human
Nutrition, Columbia University, New York, New York
100323
Received 16 January 1998/Accepted 15 April 1998
The rates of mother-to-child transmission of human immunodeficiency
virus type 1 (HIV-1), progression to AIDS following HIV-1 infection,
and AIDS-associated mortality are all inversely correlated with serum
vitamin A levels (R. D. Semba, W. T. Caiaffa, N. M. H. Graham, S. Cohn, and D. Vlahov, J. Infect. Dis. 171:1196-1202, 1995; R. D. Semba, N. M. H. Graham, W. T. Caiaffa,
J. B. Margolik, L. Clement, and D. Vlahov, Arch. Intern. Med.
153:2149-2154, 1993; R. D. Semba, P. G. Miotti, J. D. Chiphangwi, A. J. Saah, J. K. Canner, G. A. Dallabetta,
and D. R. Hoover, Lancet 343:1593-1596, 1994). Here we show that
physiological concentrations of vitamin A, as retinol or as its
metabolite, all-trans retinoic acid, repressed HIV-1Ba-L replication in monocyte-derived macrophages
(MDMs). Repression required retinoid treatment of peripheral monocytes during their in vitro differentiation into MDMs. Retinoids had no
repressive effect if they were added after virus infection. Retinol, as
well as all-trans retinoic acid and 9-cis
retinoic acid, also repressed HIV-1 long terminal repeat (LTR)-directed expression up to 200-fold in transfected THP-1 monocytes. Analysis of
HIV-1 LTR deletion mutants demonstrated that retinoids were able to
repress activation of HIV-1 expression by both NF-
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Retinoid-Induced Repression of Human
Immunodeficiency Virus Type 1 Core Promoter Activity Inhibits
Virus Replication
B and Tat. A
cis-acting sequence required for retinoid-mediated
repression of HIV-1 transcription was localized between nucleotides
51 and +12 of the HIV-1 LTR within the core promoter. Protein-DNA
cross-linking experiments identified four proteins specific to
retinoid-treated cells that bound to the core promoter. We conclude
that retinoids render macrophages resistant to virus replication by
modulating the interaction of cellular transcription factors with the
viral core promoter.
*
Corresponding author. Mailing address: Department of
Microbiology, Boston University School of Medicine, 715 Albany St.,
Boston, MA 02118. Phone: (617) 638-7790. Fax: (617) 638-4286. E-mail: gviglian{at}bu.edu.
This article has been cited by other articles:
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»