Apoptosis

, Volume 12, Issue 10, pp 1879–1892

The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells

  • Bénédicte Py
  • Jérôme Bouchet
  • Guillaume Jacquot
  • Nathalie Sol-Foulon
  • Stéphane Basmaciogullari
  • Olivier Schwartz
  • Martine Biard-Piechaczyk
  • Serge Benichou
Original Paper

DOI: 10.1007/s10495-007-0106-4

Cite this article as:
Py, B., Bouchet, J., Jacquot, G. et al. Apoptosis (2007) 12: 1879. doi:10.1007/s10495-007-0106-4

Abstract

In addition to its positive signaling function in the antigen presentation process, CD4 acts as the primary receptor for HIV-1. Contact between CD4 and the viral envelope leads to virus entry, but can also trigger apoptosis of uninfected CD4+ T-cells through a mechanism that is poorly understood. We show that Siva-1, a death domain-containing proapoptotic protein, associates with the cytoplasmic domain of CD4. This interaction is mediated by the cysteine-rich region found in the C-terminal part of the Siva-1 protein. Expression of Siva-1 specifically increases the susceptibility of both T-cell lines and unstimulated human primary CD4+ T-lymphocytes to CD4-mediated apoptosis triggered by the HIV-1 envelope, and results in activation of a caspase-dependent mitochondrial pathway. The same susceptibility is observed in T-cells expressing a truncated form of CD4 that is able to recruit Siva-1 but fails to associate with p56Lck, indicating that Siva-1 participates in a pathway independent of the p56Lck kinase activity. Altogether, these results suggest that Siva-1 might participate in the CD4-initiated signaling apoptotic pathway induced by the HIV-1 envelope in T-lymphoid cells.

Keywords

ApoptosisCD4HIV envelopeSiva-1T-lymphocytes

Abbreviations

CD4c

CD4 cytoplasmic domain

AIDS

acquired immunodeficiency syndrome

HIV

human immunodeficiency virus

DDHR

death domain homology region

FADD

Fas-associating protein with a DD

GITR

glucocorticoid-induced TNFR family-related gene

Gal4AD

Gal4 activating domain

PI

propidium iodide

PS

phosphatidyl-serine

RT

room temperature

GST

glutathione S-transferase

GSH

glutathione

SD

standard deviation

APC

antigen presenting cells

Abs

antibodies

AICD

activation-induced cell death

Supplementary material

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Bénédicte Py
    • 1
    • 2
    • 3
  • Jérôme Bouchet
    • 1
    • 2
  • Guillaume Jacquot
    • 1
    • 2
  • Nathalie Sol-Foulon
    • 4
  • Stéphane Basmaciogullari
    • 1
    • 2
  • Olivier Schwartz
    • 4
  • Martine Biard-Piechaczyk
    • 5
  • Serge Benichou
    • 1
    • 2
  1. 1.Institut Cochin, CNRS (UMR 8104)Université Paris DescartesParisFrance
  2. 2.Inserm U567ParisFrance
  3. 3.Department of Cell BiologyHarvard Medical SchoolBostonUSA
  4. 4.Institut PasteurParisFrance
  5. 5.Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121Université Montpellier 1MontpellierFrance