The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells

J Biol Chem. 2005 Nov 18;280(46):38376-82. doi: 10.1074/jbc.M506630200. Epub 2005 Sep 9.

Abstract

HIV infection and the progression to AIDS are characterized by the depletion of CD4(+) T cells through apoptosis of the uninfected bystander cells and the direct killing of HIV-infected cells. This is mediated in part by the human immunodeficiency virus, type 1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells and CD178 gene expression, which is critically involved in T cell apoptosis. The differing ability of HIV strains to induce death of infected and uninfected cells may play a role in the clinical and biological differences displayed by HIV strains. We chemically synthesized the 86-residue truncated short variant of Tat and its full-length form. We show that the trans-activation ability of Tat at the long terminal repeat does not correlate with T cell apoptosis but that the ability of Tat to up-regulate CD178 mRNA expression and induce apoptosis in T cells is critically dependent on the C terminus of Tat. Moreover, the greater 86-residue Tat-induced apoptosis is via the extrinsic pathway of CD95-CD178.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Separation
  • Fas Ligand Protein
  • Flow Cytometry
  • Gene Expression Regulation*
  • Gene Products, tat / chemistry*
  • Gene Products, tat / physiology*
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / virology
  • Membrane Glycoproteins / physiology*
  • Mutation
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / metabolism*
  • Time Factors
  • Transcriptional Activation
  • Tumor Necrosis Factors / physiology*
  • Up-Regulation
  • fas Receptor / biosynthesis

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Gene Products, tat
  • Membrane Glycoproteins
  • RNA, Messenger
  • Tumor Necrosis Factors
  • fas Receptor