Non-mitogenic T cell activation signals are sufficient for induction of human immunodeficiency virus transcription

Eur J Immunol. 1991 Jan;21(1):167-72. doi: 10.1002/eji.1830210125.

Abstract

The expression of human immunodeficiency virus type 1 (HIV) is enhanced after T cell activation due to the interaction of cell-encoded nuclear factors with binding sites in the viral long terminal repeats (LTR). We studied the minimal signal transduction requirements for induction of HIV transcription during T cell activation. Monoclonal antibodies (mAb) against the T cell receptor/CD3 complex induced interleukin (IL) 2 production as well as HIV-LTR-directed gene expression in Jurkat T cells. Addition of cyclosporin A or buffering of intracellular Ca2+ changes did not abolish this LTR-directed gene expression but did block IL 2 production. In contrast, interference with protein kinase C (PKC) activation did inhibit both IL 2 production and LTR-driven gene expression. Under all conditions HIV-LTR-directed gene expression correlated with gene expression induced by the NF-kB binding enhancer, but not by the NF-AT or OCT-1 binding sites. In accordance with observations by Verweij, Geerts and Aarden on the CD28 co-stimulatory activation of IL2 transcription via an NF-kB-like activity, stimulation of the CD2, CD28 and CD44 accessory molecules was tested to mimick physiological activation signals independent of T cell receptor triggering. mAb directed against CD2 and CD44 only marginally induced the LTR. Next, non-mitogenic stimulation by mAb against CD28 clearly induced the HIV-LTR- and NF-kB- but not NF-AT- and OCT-1-driven chloramphenicol acetyltransferase CAT expression, showing a direct effect on gene expression via this receptor. Taken together, this report shows that non-mitogenic T cell activation signals are sufficient to induce HIV transcription. The finding that these signals may be delivered by receptors that are not dependent on antigen-specific activation may have important implications for our understanding of HIV pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / physiology
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • CD28 Antigens
  • CD3 Complex
  • Calcimycin / pharmacology
  • Calcium / physiology
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Viral* / drug effects
  • HIV Long Terminal Repeat / physiology
  • HIV-1 / genetics*
  • Humans
  • In Vitro Techniques
  • Lymphocyte Activation*
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Immunologic / physiology
  • Signal Transduction / drug effects
  • T-Lymphocytes / microbiology
  • T-Lymphocytes / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD3 Complex
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Calcimycin
  • Tetradecanoylphorbol Acetate
  • Calcium