HIV elite control is associated with reduced TRAILshort expression

Ana C. Paim, Nathan W Cummins, Sekar Natesampillai, Enrique Garcia-Rivera, Nicole Kogan, Ujjwal Neogi, Anders Sönnerborg, Maike Sperk, Gary D. Bren, Steve Deeks, Eric Polley, Andrew David Badley

Research output: Contribution to journalArticle

Abstract

Objective:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) dependent apoptosis has been implicated in CD4+ T-cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression.Design:Cohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations.Methods:TRAILshort and TRAIL gene expression in peripheral blood mononuclear cells (PBMCs) was determined by RNA-seq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively.Results:HIV-1 elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P < 0.001) than viremic progressors.Conclusion:Reduced TRAILshort expression in PBMCs and plasma is associated with HIV-1 elite controller status.

Original languageEnglish (US)
Pages (from-to)1757-1763
Number of pages7
JournalAIDS
Volume33
Issue number11
DOIs
StatePublished - Sep 1 2019

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HIV-1
HIV
Blood Cells
Cell Death
HIV Infections
TNF-Related Apoptosis-Inducing Ligand
Apoptosis
Ligands
Blood Proteins
Cohort Studies
Tumor Necrosis Factor-alpha
RNA
T-Lymphocytes
Gene Expression
Antibodies
Population

Keywords

  • apoptosis
  • CD4-positive T-lymphocytes
  • HIV
  • HIV elite controllers
  • TRAILshort
  • tumor necrosis factor-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Paim, A. C., Cummins, N. W., Natesampillai, S., Garcia-Rivera, E., Kogan, N., Neogi, U., ... Badley, A. D. (2019). HIV elite control is associated with reduced TRAILshort expression. AIDS, 33(11), 1757-1763. https://doi.org/10.1097/QAD.0000000000002279

HIV elite control is associated with reduced TRAILshort expression. / Paim, Ana C.; Cummins, Nathan W; Natesampillai, Sekar; Garcia-Rivera, Enrique; Kogan, Nicole; Neogi, Ujjwal; Sönnerborg, Anders; Sperk, Maike; Bren, Gary D.; Deeks, Steve; Polley, Eric; Badley, Andrew David.

In: AIDS, Vol. 33, No. 11, 01.09.2019, p. 1757-1763.

Research output: Contribution to journalArticle

Paim, AC, Cummins, NW, Natesampillai, S, Garcia-Rivera, E, Kogan, N, Neogi, U, Sönnerborg, A, Sperk, M, Bren, GD, Deeks, S, Polley, E & Badley, AD 2019, 'HIV elite control is associated with reduced TRAILshort expression', AIDS, vol. 33, no. 11, pp. 1757-1763. https://doi.org/10.1097/QAD.0000000000002279
Paim AC, Cummins NW, Natesampillai S, Garcia-Rivera E, Kogan N, Neogi U et al. HIV elite control is associated with reduced TRAILshort expression. AIDS. 2019 Sep 1;33(11):1757-1763. https://doi.org/10.1097/QAD.0000000000002279
Paim, Ana C. ; Cummins, Nathan W ; Natesampillai, Sekar ; Garcia-Rivera, Enrique ; Kogan, Nicole ; Neogi, Ujjwal ; Sönnerborg, Anders ; Sperk, Maike ; Bren, Gary D. ; Deeks, Steve ; Polley, Eric ; Badley, Andrew David. / HIV elite control is associated with reduced TRAILshort expression. In: AIDS. 2019 ; Vol. 33, No. 11. pp. 1757-1763.
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abstract = "Objective:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) dependent apoptosis has been implicated in CD4+ T-cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression.Design:Cohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations.Methods:TRAILshort and TRAIL gene expression in peripheral blood mononuclear cells (PBMCs) was determined by RNA-seq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively.Results:HIV-1 elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P < 0.001) than viremic progressors.Conclusion:Reduced TRAILshort expression in PBMCs and plasma is associated with HIV-1 elite controller status.",
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AU - Neogi, Ujjwal

AU - Sönnerborg, Anders

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AB - Objective:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) dependent apoptosis has been implicated in CD4+ T-cell death and immunologic control of HIV-1 infection. We have described a splice variant called TRAILshort, which is a dominant negative ligand that antagonizes TRAIL-induced cell death in the context of HIV-1 infection. HIV-1 elite controllers naturally control viral replication for largely unknown reasons. Since enhanced death of infected cells might be responsible, as might occur in situations of low (or inhibited) TRAILshort, we tested whether there was an association between elite controller status and reduced levels of TRAILshort expression.Design:Cohort study comparing TRAILshort and full length TRAIL expression between HIV-1 elite controllers and viremic progressors from two independent populations.Methods:TRAILshort and TRAIL gene expression in peripheral blood mononuclear cells (PBMCs) was determined by RNA-seq. TRAILshort and TRAIL protein expression in plasma was determined by antibody bead array and proximity extension assay respectively.Results:HIV-1 elite controllers expressed less TRAILshort transcripts in PBMCs (P = 0.002) and less TRAILshort protein in plasma (P < 0.001) than viremic progressors.Conclusion:Reduced TRAILshort expression in PBMCs and plasma is associated with HIV-1 elite controller status.

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