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 D. Badley

doi:10.1097/QAD.0000000000002279

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 D. Badley

Medicine - Infectious Disease and International Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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 language	English (US)
Pages (from-to)	1757-1763
Number of pages	7
Journal	AIDS
Volume	33
Issue number	11
DOIs	https://doi.org/10.1097/QAD.0000000000002279
State	Published - Sep 1 2019

Bibliographical note

Funding Information:
The authors would like to thank the persons living with HIV who graciously participated in the studies described. A.C.P. and N.W.C. were supported through the Mayo Clinic Foundation. U.N. is supported by the Swedish Research Council establishment grant (2017-01330). S.R.L. was supported by the National Institutes of Health (NIH) Delaney AIDS Research Enterprise (DARE U19 AI096109 and UM1 AI126611-01) and the National Health and Medical Research Council (NHMRC) of Australia (NHMRC program grant and practitioner fellowship to S.R.L.). A.D.B was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health grant numbers (AI110173 and AI120698). H.-P.K. is a Markey Molecular Medicine Investigator and received support as the inaugural recipient of the JoséCarreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Fred Hutch Endowed Chair for Cell and Gene Therapy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.

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SDG 3 Good Health and Well-being

Keywords

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

PubMed: MeSH publication types

Journal Article

Publisher link

10.1097/QAD.0000000000002279

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873462

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@article{40d6584adb8f48a9a1deebf0bb6f0178,

title = "HIV elite control is associated with reduced TRAILshort expression",

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.",

keywords = "CD4-positive T-lymphocytes, HIV, HIV elite controllers, TRAILshort, apoptosis, tumor necrosis factor-related apoptosis-inducing ligand",

author = "Paim, \{Ana C.\} and Cummins, \{Nathan W.\} and Sekar Natesampillai and Enrique Garcia-Rivera and Nicole Kogan and Ujjwal Neogi and Anders S{\"o}nnerborg and Maike Sperk and Bren, \{Gary D.\} and Steve Deeks and Eric Polley and Badley, \{Andrew D.\}",

note = "Funding Information: The authors would like to thank the persons living with HIV who graciously participated in the studies described. A.C.P. and N.W.C. were supported through the Mayo Clinic Foundation. U.N. is supported by the Swedish Research Council establishment grant (2017-01330). S.R.L. was supported by the National Institutes of Health (NIH) Delaney AIDS Research Enterprise (DARE U19 AI096109 and UM1 AI126611-01) and the National Health and Medical Research Council (NHMRC) of Australia (NHMRC program grant and practitioner fellowship to S.R.L.). A.D.B was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health grant numbers (AI110173 and AI120698). H.-P.K. is a Markey Molecular Medicine Investigator and received support as the inaugural recipient of the Jos{\'e}Carreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Fred Hutch Endowed Chair for Cell and Gene Therapy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Publisher Copyright: {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2019",

month = sep,

day = "1",

doi = "10.1097/QAD.0000000000002279",

language = "English (US)",

volume = "33",

pages = "1757--1763",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "11",

}

TY - JOUR

T1 - HIV elite control is associated with reduced TRAILshort expression

AU - Paim, Ana C.

AU - Cummins, Nathan W.

AU - Natesampillai, Sekar

AU - Garcia-Rivera, Enrique

AU - Kogan, Nicole

AU - Neogi, Ujjwal

AU - Sönnerborg, Anders

AU - Sperk, Maike

AU - Bren, Gary D.

AU - Deeks, Steve

AU - Polley, Eric

AU - Badley, Andrew D.

N1 - Funding Information: The authors would like to thank the persons living with HIV who graciously participated in the studies described. A.C.P. and N.W.C. were supported through the Mayo Clinic Foundation. U.N. is supported by the Swedish Research Council establishment grant (2017-01330). S.R.L. was supported by the National Institutes of Health (NIH) Delaney AIDS Research Enterprise (DARE U19 AI096109 and UM1 AI126611-01) and the National Health and Medical Research Council (NHMRC) of Australia (NHMRC program grant and practitioner fellowship to S.R.L.). A.D.B was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health grant numbers (AI110173 and AI120698). H.-P.K. is a Markey Molecular Medicine Investigator and received support as the inaugural recipient of the JoséCarreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Fred Hutch Endowed Chair for Cell and Gene Therapy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Publisher Copyright: © 2019 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

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.

KW - CD4-positive T-lymphocytes

KW - HIV

KW - HIV elite controllers

KW - TRAILshort

KW - apoptosis

KW - tumor necrosis factor-related apoptosis-inducing ligand

UR - https://www.scopus.com/pages/publications/85069923697

UR - https://www.scopus.com/pages/publications/85069923697#tab=citedBy

U2 - 10.1097/QAD.0000000000002279

DO - 10.1097/QAD.0000000000002279

M3 - Article

C2 - 31149947

AN - SCOPUS:85069923697

SN - 0269-9370

VL - 33

SP - 1757

EP - 1763

JO - AIDS

JF - AIDS

IS - 11

ER -

HIV elite control is associated with reduced TRAILshort expression

Abstract

Bibliographical note

UN SDGs

Keywords

PubMed: MeSH publication types

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