Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes

C. Parrott, T. Seidner, E. Duh, J. Leonard, T. S. Theodore, A. Buckler-White, M. A. Martin, A. B. Rabson

Research output: Contribution to journalArticle

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Abstract

The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains three binding sites for the transcriptional factor Sp1. In order to investigate the role that the Sp1-binding sites play in regulation of H1V replication, we have introduced a deletion of all three Sp1-binding sites into the LTR of an infectious molecular clone of HIV. Viral stocks have been prepared from this mutant virus, designated dl-Sp, and these stocks have been used to study its replicative ability in human T cells. The dl-Sp virus replicated efficiently in MT4 cells and in phytohemagglutinin-stimulated human peripheral blood lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T cells unless those cells had been treated with the cytokine tumor necrosis factor α. Gel retardation assays to study the levels of DNA-binding proteins present in these cells showed that NF-κB activity could he detected in the nuclei of MT4 cells hut not in A3.01 cells unless they had heen treated with tumor necrosis factor α. Thus, the presence of NF-κB activity appeared to be required for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted. This suggests that NF-κB can functionally compensate for Sp1 in activating HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units of other viruses in that it is composed of multiple functional elements that may contrihute differently to viral replication depending on the levels of DNA-binding proteins present in the target cells.

Original languageEnglish (US)
Pages (from-to)1414-1419
Number of pages6
JournalJournal of virology
Volume65
Issue number3
StatePublished - Jan 1 1991
Externally publishedYes

Fingerprint

terminal repeat sequences
Terminal Repeat Sequences
Human immunodeficiency virus
Virus Replication
virus replication
HIV Long Terminal Repeat
binding sites
T-lymphocytes
Binding Sites
HIV
T-Lymphocytes
DNA-binding proteins
tumor necrosis factors
DNA-Binding Proteins
Viruses
viruses
cells
Tumor Necrosis Factor-alpha
phytohemagglutinin
Phytohemagglutinins

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Parrott, C., Seidner, T., Duh, E., Leonard, J., Theodore, T. S., Buckler-White, A., ... Rabson, A. B. (1991). Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes. Journal of virology, 65(3), 1414-1419.
Parrott, C. ; Seidner, T. ; Duh, E. ; Leonard, J. ; Theodore, T. S. ; Buckler-White, A. ; Martin, M. A. ; Rabson, A. B. / Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes. In: Journal of virology. 1991 ; Vol. 65, No. 3. pp. 1414-1419.
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Parrott, C, Seidner, T, Duh, E, Leonard, J, Theodore, TS, Buckler-White, A, Martin, MA & Rabson, AB 1991, 'Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes', Journal of virology, vol. 65, no. 3, pp. 1414-1419.

Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes. / Parrott, C.; Seidner, T.; Duh, E.; Leonard, J.; Theodore, T. S.; Buckler-White, A.; Martin, M. A.; Rabson, A. B.

In: Journal of virology, Vol. 65, No. 3, 01.01.1991, p. 1414-1419.

Research output: Contribution to journalArticle

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N2 - The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains three binding sites for the transcriptional factor Sp1. In order to investigate the role that the Sp1-binding sites play in regulation of H1V replication, we have introduced a deletion of all three Sp1-binding sites into the LTR of an infectious molecular clone of HIV. Viral stocks have been prepared from this mutant virus, designated dl-Sp, and these stocks have been used to study its replicative ability in human T cells. The dl-Sp virus replicated efficiently in MT4 cells and in phytohemagglutinin-stimulated human peripheral blood lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T cells unless those cells had been treated with the cytokine tumor necrosis factor α. Gel retardation assays to study the levels of DNA-binding proteins present in these cells showed that NF-κB activity could he detected in the nuclei of MT4 cells hut not in A3.01 cells unless they had heen treated with tumor necrosis factor α. Thus, the presence of NF-κB activity appeared to be required for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted. This suggests that NF-κB can functionally compensate for Sp1 in activating HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units of other viruses in that it is composed of multiple functional elements that may contrihute differently to viral replication depending on the levels of DNA-binding proteins present in the target cells.

AB - The long terminal repeat (LTR) of the human immunodeficiency virus (HIV) contains three binding sites for the transcriptional factor Sp1. In order to investigate the role that the Sp1-binding sites play in regulation of H1V replication, we have introduced a deletion of all three Sp1-binding sites into the LTR of an infectious molecular clone of HIV. Viral stocks have been prepared from this mutant virus, designated dl-Sp, and these stocks have been used to study its replicative ability in human T cells. The dl-Sp virus replicated efficiently in MT4 cells and in phytohemagglutinin-stimulated human peripheral blood lymphocytes, but it replicated poorly and with delayed kinetics in A3.01 (CEM) T cells unless those cells had been treated with the cytokine tumor necrosis factor α. Gel retardation assays to study the levels of DNA-binding proteins present in these cells showed that NF-κB activity could he detected in the nuclei of MT4 cells hut not in A3.01 cells unless they had heen treated with tumor necrosis factor α. Thus, the presence of NF-κB activity appeared to be required for efficient replication of an HIV whose LTR Sp1-binding sites had been deleted. This suggests that NF-κB can functionally compensate for Sp1 in activating HIV replication. The HIV LTR is therefore similar to the promoter-enhancer units of other viruses in that it is composed of multiple functional elements that may contrihute differently to viral replication depending on the levels of DNA-binding proteins present in the target cells.

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Parrott C, Seidner T, Duh E, Leonard J, Theodore TS, Buckler-White A et al. Variable role of the long terminal repeat Sp-1-binding sites in human immunodeficiency virus replication in T lymphocytes. Journal of virology. 1991 Jan 1;65(3):1414-1419.