Original Paper

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 PyAffiliated withInstitut Cochin, CNRS (UMR 8104), Université Paris DescartesInserm U567Department of Cell Biology, Harvard Medical School
  • , Jérôme BouchetAffiliated withInstitut Cochin, CNRS (UMR 8104), Université Paris DescartesInserm U567
  • , Guillaume JacquotAffiliated withInstitut Cochin, CNRS (UMR 8104), Université Paris DescartesInserm U567
  • , Nathalie Sol-FoulonAffiliated withInstitut Pasteur
  • , Stéphane BasmaciogullariAffiliated withInstitut Cochin, CNRS (UMR 8104), Université Paris DescartesInserm U567
  • , Olivier SchwartzAffiliated withInstitut Pasteur
  • , Martine Biard-PiechaczykAffiliated withLaboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS UMR 5121, Université Montpellier 1
  • , Serge BenichouAffiliated withInstitut Cochin, CNRS (UMR 8104), Université Paris DescartesInserm U567 Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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

Apoptosis CD4 HIV envelope Siva-1 T-lymphocytes