title: 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.
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Program in Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: David J
authors.initials: DJ
authors.lastname: Schnepple
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Brett
authors.initials: B
authors.lastname: Shepard
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Bren
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Program in Translational Immunovirology and Biodefense, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Cummins
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Sekar
authors.initials: S
authors.lastname: Natesampillai
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Sergey
authors.initials: S
authors.lastname: Trushin
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Alicia
authors.initials: A
authors.lastname: Algeciras-Schimnich
authors.affiliation: Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Xue W
authors.initials: XW
authors.lastname: Meng
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Sainski
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Rizza
authors.affiliation: Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905; Program in Translational Immunovirology and Biodefense, Mayo Clinic College of Medicine, Rochester, Minnesota 55905. Electronic address: badley.andrew@mayo.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Badley
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006678:HIV; D015658:HIV Infections / Q000097:blood* / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human