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

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
DOIs
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Parrott, C., Seidner, T., Duh, E., Leonard, J., Theodore, T. S., Buckler-White, A., Martin, M. 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. https://doi.org/10.1128/jvi.65.3.1414-1419.1991