Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat

S. E. Tong-Starksen, Paul A Luciw, B. M. Peterlin

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Abstract

The state of T cell activation and proliferation controls HIV-1 replication and gene expression. Previously, we demonstrated that the administration of PHA and PMA to the human T cell line Jurkat activates the HIV-1 enhancer, which is composed of two nuclear factor κB (NFκB) binding sites. Here, we show that PMA alone is sufficient for this effect. In addition, activation of T cells through the surface proteins TCR/CD3 and CD28 increased gene expression directed by the HIV-1 long terminal repeat (LTR) to the same extent as PMA. Analysis of 5' deletions in the LTR revealed that the NFκB binding sites and sequences in the upstream U3 region are required for this response. Whereas cyclosporin A did not inhibit the effect of PMA, it reduced the effects of agonists to TCR/CD3 and CD28 on the LTR. H7, an inhibitor of protein kinase C (PKC), blocked the effects of all stimuli. Thus, PMA activates the NFκB sites through a PKC-dependent pathway while ligands to TCR/CD3 and CD28 activate the LTR through a cyclosporin A-sensitive, PKC-dependent pathway of T cell activation. We conclude that mechanisms involved in the expression of IL-2 and the α-chain of the IL-2Rα genes also play a role in the regulation of HIV-1. Physiologic stimuli can activate HIV-1 gene expression; agents that block T cell activation also inhibit activation of the LTR. These observations might serve as a model for the regulation of HIV-1 gene expression in peripheral blood T cells.

Original languageEnglish (US)
Pages (from-to)702-707
Number of pages6
JournalJournal of Immunology
Volume142
Issue number2
StatePublished - 1989

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HIV Long Terminal Repeat
HIV-1
Membrane Proteins
Terminal Repeat Sequences
T-Lymphocytes
Protein Kinase C
Gene Expression
HIV Enhancer
Cyclosporine
Binding Sites
Interleukin-2
Blood Cells
Cell Proliferation
Ligands
Cell Line
Genes

ASJC Scopus subject areas

  • Immunology

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Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat. / Tong-Starksen, S. E.; Luciw, Paul A; Peterlin, B. M.

In: Journal of Immunology, Vol. 142, No. 2, 1989, p. 702-707.

Research output: Contribution to journalArticle

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