Isolation of a TRAIL antagonist from the serum of HIV-infected patients

David J. Schnepple, Brett Shepard, Gary D. Bren, Nathan W Cummins, Sekar Natesampillai, Sergey Trushin, Alicia Algeciras-Schimnich, Xue W. Meng, Amy M. Sainski, Stacey Rizza, Scott H Kaufmann, Andrew David Badley

Research output: Contribution to journalArticle

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Abstract

Virus-host interactions are characterized by the selection of adaptive mechanisms by which to evade pathogenic and defense mechanisms, respectively. In primary T cells infected with HIV, HIV infection up-regulates TNF-related apoptosis inducing ligand (TRAIL) and death-inducing TRAIL receptors, but blockade of TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead, HIV infection results in a novel splice variant that we call TRAIL-short (TRAIL-s), which antagonizes TRAIL-R2. In HIV patients, plasma TRAIL-s concentration increases with increasing viral load and renders cells resistant to TRAIL-induced death. Knockdown of TRAIL-s abrogates this resistance. We propose that TRAIL-s is a novel adaptive mechanism of apoptosis resistance acquired by HIV-infected cells to avoid their elimination by TRAIL-dependent effector mechanism.

Original languageEnglish (US)
Pages (from-to)35742-35754
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number41
DOIs
StatePublished - Oct 14 2011

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
HIV
Serum
TNF-Related Apoptosis-Inducing Ligand Receptors
HIV Infections
T-cells
Cell death
Viral Load
Viruses
Cell Death
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Isolation of a TRAIL antagonist from the serum of HIV-infected patients. / Schnepple, David J.; Shepard, Brett; Bren, Gary D.; Cummins, Nathan W; Natesampillai, Sekar; Trushin, Sergey; Algeciras-Schimnich, Alicia; Meng, Xue W.; Sainski, Amy M.; Rizza, Stacey; Kaufmann, Scott H; Badley, Andrew David.

In: Journal of Biological Chemistry, Vol. 286, No. 41, 14.10.2011, p. 35742-35754.

Research output: Contribution to journalArticle

Schnepple, DJ, Shepard, B, Bren, GD, Cummins, NW, Natesampillai, S, Trushin, S, Algeciras-Schimnich, A, Meng, XW, Sainski, AM, Rizza, S, Kaufmann, SH & Badley, AD 2011, 'Isolation of a TRAIL antagonist from the serum of HIV-infected patients', Journal of Biological Chemistry, vol. 286, no. 41, pp. 35742-35754. https://doi.org/10.1074/jbc.M111.274639
Schnepple DJ, Shepard B, Bren GD, Cummins NW, Natesampillai S, Trushin S et al. Isolation of a TRAIL antagonist from the serum of HIV-infected patients. Journal of Biological Chemistry. 2011 Oct 14;286(41):35742-35754. https://doi.org/10.1074/jbc.M111.274639
Schnepple, David J. ; Shepard, Brett ; Bren, Gary D. ; Cummins, Nathan W ; Natesampillai, Sekar ; Trushin, Sergey ; Algeciras-Schimnich, Alicia ; Meng, Xue W. ; Sainski, Amy M. ; Rizza, Stacey ; Kaufmann, Scott H ; Badley, Andrew David. / Isolation of a TRAIL antagonist from the serum of HIV-infected patients. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 41. pp. 35742-35754.
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