Evidence map›Paper›PMID 34962974›Full record

ArticlePLoS pathogens2021

Intragenic proviral elements support transcription of defective HIV-1 proviruses.

Jeffrey Kuniholm, Elise Armstrong, Brandy Bernabe, Carolyn Coote, Anna Berenson, Samantha D Patalano, Alex Olson, Xianbao He, Nina H Lin, Juan I Fuxman Bass and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

20 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  7. Review
  8. HIV reservoirs in lymphomagenesis: hidden driver in the era of viral suppression?Microbiology and molecular biology reviews : MMBR · 2025
    Review
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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

11 authors at 1 institution in 1 country.

Jeffrey KuniholmBoston University School of Medicine, Department of Microbiology, Boston, Massachusetts, United States of America.
Elise ArmstrongBoston University School of Medicine, Department of Medicine, Section of Infectious Diseases; Boston, Massachusetts, United States of America.ORCID 0000-0002-2762-5006
Brandy BernabeBoston University School of Medicine Graduate Medical Sciences, Boston, Massachusetts, United States of America.ORCID 0000-0002-5723-2537
Carolyn CooteBoston University School of Medicine, Department of Medicine, Section of Infectious Diseases; Boston, Massachusetts, United States of America.ORCID 0000-0002-1177-7881
Anna BerensonBoston University, Department of Biology, Boston, Massachusetts, United States of America.ORCID 0000-0002-3782-6186
Samantha D PatalanoBoston University, Department of Biology, Boston, Massachusetts, United States of America.ORCID 0000-0002-8587-7981
Alex OlsonBoston University School of Medicine, Department of Medicine, Section of Infectious Diseases; Boston, Massachusetts, United States of America.ORCID 0000-0002-3371-3213
Xianbao HeBoston University School of Medicine, Department of Medicine, Section of Infectious Diseases; Boston, Massachusetts, United States of America.
Nina H LinBoston University School of Medicine, Department of Medicine, Section of Infectious Diseases; Boston, Massachusetts, United States of America.
Juan I Fuxman BassBoston University, Department of Biology, Boston, Massachusetts, United States of America.ORCID 0000-0001-9457-1207
Andrew J HendersonBoston University School of Medicine, Department of Microbiology, Boston, Massachusetts, United States of America.ORCID 0000-0002-9299-5302
Boston University · US

Funding

Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI CURT G BECKWITH, DEBBIE M. CHENG · 1998 to 2026
$51.7M
RESEARCH TRAINING IN IMMUNOLOGYT32AI007309 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI GUMMULURU, SURYARAM · 1988 to 2024
$7.4M
Structure and Function of Immune Gene Regulatory NetworksR35GM128625 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Juan Ignacio Fuxman Bass · 2018 to 2026
$4.0M
Persistent HIV-1 expression and microglia dysfunctionR01DA055488 · NIDA · BOSTON MEDICAL CENTER · PI GUMMULURU, SURYARAM, HENDERSON, ANDREW J · 2021 to 2025
$3.7M
Single nuclei transcriptomics of Alzheimer's brain diseaseR61DA047032 · NIDA · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI CHENG, CHRISTINE, HENDERSON, ANDREW J · 2018 to 2020
$3.5M
Signals that establish and maintain HIV latencyR01AI138960 · NIAID · BOSTON MEDICAL CENTER · PI HENDERSON, ANDREW J · 2018 to 2022
$2.2M
Effect of opioid use disorder on HIV latent reservoirs and immune dysfunction assessed by single-cell transcriptomicsR33DA047032 · NIDA · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI CHENG, CHRISTINE, HENDERSON, ANDREW J · 2021 to 2022
$1.8M
BU PREPR25GM125511 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI HENDERSON, ANDREW J, SCHON, KARIN · 2020 to 2024
$1.4M
NIAID NIH HHS P30 AI042853NIAID NIH HHS R01 AI138960NIAID NIH HHS T32 AI007309NIDA NIH HHS R01 DA055488NIDA NIH HHS R33 DA047032NIDA NIH HHS R61 DA047032NIGMS NIH HHS R25 GM125511NIGMS NIH HHS R35 GM128625
6 · The paper itself

Abstract

HIV-1 establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription droplet digital PCR identified env and nef transcripts which lacked 5' untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5'UTR-deficient env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5' rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH.

Indexed as

env Gene Products, Human Immunodeficiency VirusGenome, ViralHIV-1HIV InfectionsHumansMacrophagesnef Gene Products, Human Immunodeficiency VirusPolymerase Chain ReactionProvirusesRNA, ViralTranscription, Geneticenv Gene Products, Human Immunodeficiency Virusnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1RNA, Viral

Identifiers

PMID34962974
PMCPMC8746790
OpenAlexW4226149540

What OpenQuestion holds

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LicenceCC BY
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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.