Evidence map›Paper›PMID 26378236›Full record

ArticleThe Journal of biological chemistry2015

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency.

Huachao Huang, Netty Santoso, Derek Power, Sydney Simpson, Michael Dieringer, Hongyu Miao, Katerina Gurova, Chou-Zen Giam, Stephen J Elledge, Jian Zhu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

43 citing papers in PubMed, 58 citations in OpenAlex.

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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

10 authors at 5 institutions in 1 country.

Huachao HuangDepartments of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
Netty SantosoDepartments of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
Derek PowerDepartments of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642.
Sydney Simpsonthe School of Arts and Sciences, University of Rochester, Rochester, New York 14627.
Michael Dieringerthe School of Arts and Sciences, University of Rochester, Rochester, New York 14627.
Hongyu MiaoDepartment of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642.
Katerina GurovaDepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Chou-Zen GiamDepartment of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Stephen J Elledgethe Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02115; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Jian ZhuDepartments of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642; Departments of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642. Electronic address: Jian_Zhu@urmc.rochester.edu.
University of Rochester Medical Center · USUniversity of Rochester · USBrigham and Women's Hospital · USRoswell Park Comprehensive Cancer Center · USUniformed Services University of the Health Sciences · US

Funding

Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
Role of FACT Proteins in Regulating HIV Transcription and LatencyR01GM117838 · NIGMS · UNIVERSITY OF ROCHESTER · PI ZHU, JIAN · 2015 to 2018
$1.2M
Cooperation of BRD4 and TAT Associated Proteins in HIV Transcription and LatencyR33AI116180 · NIAID · UNIVERSITY OF ROCHESTER · PI ZHU, JIAN · 2016 to 2018
$1.2M
Cooperation of BRD4 and TAT Associated Proteins in HIV Transcription and LatencyR21AI116180 · NIAID · UNIVERSITY OF ROCHESTER · PI ZHU, JIAN · 2014 to 2015
$421k
NIAID NIH HHS P30 AI078498NIAID NIH HHS P30AI078498NIAID NIH HHS R21 AI116180NIAID NIH HHS R21AI116180NIAID NIH HHS R33 AI116180NIGMS NIH HHS R01 GM117838NIGMS NIH HHS R01GM117838
6 · The paper itself

Abstract

Our functional genomic RNAi screens have identified the protein components of the FACT (facilitates chromatin transcription) complex, SUPT16H and SSRP1, as top host factors that negatively regulate HIV-1 replication. FACT interacts specifically with histones H2A/H2B to affect assembly and disassembly of nucleosomes, as well as transcription elongation. We further investigated the suppressive role of FACT proteins in HIV-1 transcription. First, depletion of SUPT16H or SSRP1 protein enhances Tat-mediated HIV-1 LTR (long terminal repeat) promoter activity. Second, HIV-1 Tat interacts with SUPT16H but not SSRP1 protein. However, both SUPT16H and SSRP1 are recruited to LTR promoter. Third, the presence of SUPT16H interferes with the association of Cyclin T1 (CCNT1), a subunit of P-TEFb, with the Tat-LTR axis. Removing inhibitory mechanisms to permit HIV-1 transcription is an initial and key regulatory step to reverse post-integrated latent HIV-1 proviruses for purging of reservoir cells. We therefore evaluated the role of FACT proteins in HIV-1 latency and reactivation. Depletion of SUPT16H or SSRP1 protein affects both HIV-1 transcriptional initiation and elongation and spontaneously reverses latent HIV-1 in U1/HIV and J-LAT cells. Similar effects were observed with a primary CD4+ T cell model of HIV-1 latency. FACT proteins also interfere with HTLV-1 Tax-LTR-mediated transcription and viral latency, indicating that they may act as general transcriptional suppressors for retroviruses. We conclude that FACT proteins SUPT16H and SSRP1 play a key role in suppressing HIV-1 transcription and promoting viral latency, which may serve as promising gene targets for developing novel HIV-1 latency-reversing agents.

Indexed as

CD4-Positive T-LymphocytesCell Cycle ProteinsCell LineCyclin TDNA-Binding ProteinsHEK293 CellsHigh Mobility Group ProteinsHIV-1HIV Long Terminal RepeatHost-Pathogen InteractionsHumansHuman T-lymphotropic virus 1Models, BiologicalPositive Transcriptional Elongation Factor BPromoter Regions, GeneticRNA InterferenceCCNT1 protein, humanCell Cycle ProteinsCyclin TDNA-Binding ProteinsHigh Mobility Group ProteinsPositive Transcriptional Elongation Factor BSSRP1 protein, humanSUPT16H protein, humanTranscriptional Elongation FactorsTranscription FactorsCD4 T cellFACT complexhost-pathogen interactionhuman immunodeficiency virus (HIV)latencyRNA interference (RNAi)SSRP1SUPT16Htranscription repressorviral transcription

Identifiers

PMID26378236
PMCPMC4646377
OpenAlexW2168539009

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.