Evidence map›Paper›PMID 26355217›Full record

ArticleCell host & microbe2015

BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency.

Lars Pache, Miriam S Dutra, Adam M Spivak, John M Marlett, Jeffrey P Murry, Young Hwang, Ana M Maestre, Lara Manganaro, Mitchell Vamos, Peter Teriete and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell host & microbe, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  17. Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025
    Review
  18. Article
  19. Article
  20. Review

52 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 2 countries.

Lars PacheInfectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Miriam S DutraInfectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Adam M SpivakDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
John M MarlettNomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jeffrey P MurryNomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Young HwangDepartment of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Ana M MaestreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Lara ManganaroDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Mitchell VamosCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Peter TerieteCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Laura J MartinsDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
Renate KönigInfectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Paul-Ehrlich-Institut, Paul-Ehrlich-Strasse 51-59, 63225 Langen, Germany; German Center for Infection Research (DZIF), 63225 Langen, Germany.
Viviana SimonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alberto BosqueDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
Ana Fernandez-SesmaDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nicholas D P CosfordCell Death and Survival Networks Research Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Frederic D BushmanDepartment of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
John A T YoungNomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Vicente PlanellesDivision of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
Sumit K ChandaInfectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: schanda@sbpdiscovery.org.
Discovery Institute · USIcahn School of Medicine at Mount Sinai · USUniversity of Utah · USSalk Institute for Biological Studies · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
Molecular Virology and Systems Biology Screening CoreP01AI090935 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI YOUNG, JOHN A T · 2010 to 2014
$20.4M
Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
A Systems-level Approach to Studying HIV/AIDS Susceptibility and Substance AbuseR01DA033773 · NIDA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 2012 to 2016
$4.6M
MODULATION OF INNATE AND ADAPTIVE IMMUNITY BY DENGUE VIRUSR01AI073450 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FERNANDEZ-SESMA, ANA · 2008 to 2017
$3.3M
The Effects of ART on Platelets and HIV-Associated ThrombosisR01HL126547 · NHLBI · UNIVERSITY OF UTAH · PI PLANELLES, VICENTE, RONDINA, MATTHEW THOMAS · 2014 to 2017
$3.0M
An Ex Vivo Model of HIV-1 Latency and Reactivation using Primary Memory CellsR01AI087508 · NIAID · UNIVERSITY OF UTAH · PI PLANELLES, VICENTE · 2010 to 2014
$1.8M
ANTIBODY CATALYZED POLYMERIZATION AND GLYCOSYLATIONF32AI009093 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLANAGAN, MARK E · 1994 to 1996
–
NHLBI NIH HHS R01 HL126547NIAID NIH HHS 5R01 AI073450NIAID NIH HHS F32 AI009093NIAID NIH HHS HHSN272201400008CNIAID NIH HHS P01 AI090935NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI052845NIAID NIH HHS R01 AI073450NIAID NIH HHS R01 AI087508NIDA NIH HHS R01 DA033773PHS HHS HHSN272201400008C
6 · The paper itself

Abstract

Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed. Employing a targeted RNAi screen, we identified the ubiquitin ligase BIRC2 (cIAP1), a repressor of the noncanonical NF-κB pathway, as a potent negative regulator of LTR-dependent HIV-1 transcription. Depletion of BIRC2 through treatment with small molecule antagonists known as Smac mimetics enhanced HIV-1 transcription, leading to a reversal of latency in a JLat latency model system. Critically, treatment of resting CD4+ T cells isolated from ART-suppressed patients with the histone deacetylase inhibitor (HDACi) panobinostat together with Smac mimetics resulted in synergistic activation of the latent reservoir. These data implicate Smac mimetics as useful agents for shock-and-kill strategies to eliminate the latent HIV reservoir.

Indexed as

Gene Expression Regulation, ViralHost-Pathogen InteractionsCD4-Positive T-LymphocytesCells, CulturedHIV-1HumansHydroxamic AcidsIndolesInhibitor of Apoptosis ProteinsOligopeptidesPanobinostatTranscription, GeneticUbiquitin-Protein LigasesVirus ActivationVirus LatencyBIRC2 protein, humanHydroxamic AcidsIndolesInhibitor of Apoptosis ProteinsOligopeptidesPanobinostatSMAC peptideUbiquitin-Protein Ligases

Identifiers

PMID26355217
PMCPMC4617541
OpenAlexW1866327060

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.