Evidence map›Paper›PMID 28416661›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART.

Ann Wiegand, Jonathan Spindler, Feiyu F Hong, Wei Shao, Joshua C Cyktor, Anthony R Cillo, Elias K Halvas, John M Coffin, John W Mellors, Mary F Kearney

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed
10.6field-weighted citation impact, top 1% 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

127 citing papers in PubMed, 174 citations in OpenAlex.

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67 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

10 authors at 4 institutions in 1 country.

Ann WiegandHIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702.
Jonathan SpindlerHIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702.
Feiyu F HongDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Wei ShaoLeidos Biomedical Research, Inc., Frederick National Laboratories for Cancer Research, Frederick, MD 21702.
Joshua C CyktorDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Anthony R CilloDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Elias K HalvasDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
John M CoffinDepartment of Molecular Biology and Microbiology, Tufts University, Boston, MA 02111 kearneym@mail.nih.gov john.coffin@tufts.edu.
John W MellorsDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15261.
Mary F KearneyHIV Dynamics and Replication Program, National Cancer Institute, Frederick, MD 21702; kearneym@mail.nih.gov john.coffin@tufts.edu.
University of Pittsburgh · USNational Cancer Institute · USLeidos (United States) · USTufts University · US

Funding

Dynamics and Genetics of HIV Proviruses Before and During Antiretroviral TherapyZIABC011681 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEARNEY, MARY · 2016 to 2025
$9.3M
Quantify the Fraction of Proviruses That Express HIV RNA to Better Understand Proviral Latency and Its ReversalZIABC011698 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KEARNEY, MARY · 2016 to 2025
$5.1M
Characterizing HIV-1 diversity, evolution, and integration sites in children initiating cART in early infectionU01CA200441 · NCI · STELLENBOSCH UNIVERSITY · PI KEARNEY, MARY, VAN ZYL, GERT UVES · 2015 to 2019
$842k
NCI NIH HHS U01 CA200441
6 · The paper itself

Abstract

Little is known about the fraction of human immunodeficiency virus type 1 (HIV-1) proviruses that express unspliced viral RNA in vivo or about the levels of HIV RNA expression within single infected cells. We developed a sensitive cell-associated HIV RNA and DNA single-genome sequencing (CARD-SGS) method to investigate fractional proviral expression of HIV RNA (1.3-kb fragment of p6, protease, and reverse transcriptase) and the levels of HIV RNA in single HIV-infected cells from blood samples obtained from individuals with viremia or individuals on long-term suppressive antiretroviral therapy (ART). Spiking experiments show that the CARD-SGS method can detect a single cell expressing HIV RNA. Applying CARD-SGS to blood mononuclear cells in six samples from four HIV-infected donors (one with viremia and not on ART and three with viremia suppressed on ART) revealed that an average of 7% of proviruses (range: 2-18%) expressed HIV RNA. Levels of expression varied from one to 62 HIV RNA molecules per cell (median of 1). CARD-SGS also revealed the frequent expression of identical HIV RNA sequences across multiple single cells and across multiple time points in donors on suppressive ART consistent with constitutive expression of HIV RNA in infected cell clones. Defective proviruses were found to express HIV RNA at levels similar to those proviruses that had no obvious defects. CARD-SGS is a useful tool to characterize fractional proviral expression in single infected cells that persist despite ART and to assess the impact of experimental interventions on proviral populations and their expression.

Indexed as

Anti-Retroviral AgentsFemaleGene Expression Regulation, ViralHIV-1HumansLeukocytes, MononuclearMaleProvirusesRNA, ViralTranscription, GeneticAnti-Retroviral AgentsRNA, ViralCARD-SGSHIV expressionpersistence on ARTproviral expressionsingle-cell analysis

Identifiers

PMID28416661
PMCPMC5422779
OpenAlexW2606857030

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.