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

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.

SUBMITTER: Schnepple DJ

PROVIDER: S-EPMC3195643 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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

Schnepple David J DJ Shepard Brett B Bren Gary D GD Cummins Nathan W NW Natesampillai Sekar S Trushin Sergey S Algeciras-Schimnich Alicia A Meng Xue W XW Sainski Amy M AM Rizza Stacey A SA Kaufmann Scott H SH Badley Andrew D AD

The Journal of biological chemistry 20110822 41

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 ...[more]

PMID: 21859711

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

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

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