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The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells.
Py B., Bouchet J., Jacquot G., Sol-Foulon N., Basmaciogullari S., Schwartz O., Biard-Piechaczyk M., Benichou S.
APOPTOSIS 12, 10 (2007) 1879-92 - http://hal.archives-ouvertes.fr/hal-00257277
Sciences du Vivant/Biochimie, Biologie Moléculaire
(17653867)
The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells.
Bénédicte Py1, Jérôme Bouchet1, Guillaume Jacquot1, Nathalie Sol-Foulon2, Stéphane Basmaciogullari1, Olivier Schwartz2, Martine Biard-Piechaczyk3, Serge Benichou1
1 :  IC - Institut Cochin
http://www.cochin.inserm.fr
CNRS : UMR8104 – INSERM : U567 – Université Paris V - Paris Descartes
Direction,services Communs,plateformes Bâtiment MECHAIN 22 rue Méchain 75014 PARIS
France
2 :  Virus et Immunité
CNRS : URA1930 – Institut Pasteur de Paris
28, rue du docteur Roux F-75724 Paris cedex 15
France
3 :  CPBS - Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé
Université Montpellier I – CNRS : UMR5236 – Université Montpellier II - Sciences et techniques
Institut de Biologie CS 69033 4 boulevard Henri IV 34965 MONTPELLIER Cedex 2
France
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.
Anglais

Articles dans des revues avec comité de lecture
10.1007/s10495-007-0106-4
Apoptosis (Apoptosis)
Publisher Springer Verlag (Germany)
ISSN 1360-8185 (eISSN : 1573-675X)
non spécifiée
10/2007
12
10
1879-92