Evidence map›Paper›PMID 33176710›Full record

ArticleBMC immunology2020

Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients.

Sukrutha Chettimada, David R Lorenz, Vikas Misra, Steven M Wolinsky, Dana Gabuzda

Open access · goldAbstract read
In one paragraph

Article in BMC immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.2field-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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  13. The miRNomics of antiretroviral therapy-induced obesity.Functional & integrative genomics · 2025
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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

5 authors at 3 institutions in 1 country.

Sukrutha ChettimadaDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
David R LorenzDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Vikas MisraDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Steven M WolinskyDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Dana GabuzdaDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. dana_gabuzda@dfci.harvard.edu.ORCID 0000-0002-4964-5083
Dana-Farber Cancer Institute · USHarvard University · USNorthwestern University · US

Funding

NATURAL HISTORY OF AIDS IN HOMOSEXUAL MENU01AI035040 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DETELS, ROGER, MARTINEZ-MAZA, OTONIEL · 1993 to 2018
$75.2M
University of Pittsburgh Multicenter AIDS Cohort Study (MACS)U01AI035041 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARTINSON, JEREMY JAMES, RINALDO, CHARLES R · 1993 to 2018
$71.4M
MULTICENTER AIDS COHORT STUDYU01AI035039 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 1993 to 2018
$66.4M
Multicenter Aids Cohort Study- Part B (Baltimore Site)U01AI035042 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T, MARGOLICK, JOSEPH B. · 1993 to 2018
$61.5M
QAQC Johns Hopkins Institute for Clinical and Translational ResearchUL1TR003098 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2019 to 2023
$57.7M
Sex differences in the role of multi-omicsin HIV-associated carotid artery atherosclerosisU01HL146193 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Stephen J Gange, Elizabeth Topper · 2019 to 2026
$35.8M
Northwestern CORE Clinical Research Site: Trans-omics for HIV/AIDS ResearchU01HL146240 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Frank J Palella, Valentina Stosor · 2019 to 2026
$31.5M
Center for the Analysis & Management of the Multicenter AIDS Cohort StudyUM1AI035043 · NIAID · JOHNS HOPKINS UNIVERSITY · PI D'SOUZA, GYPSYAMBER, JACOBSON, LISA P · 2012 to 2018
$20.7M
The Manhattan HIV Brain BankU24MH100931 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MORGELLO, SUSAN · 2013 to 2023
$14.0M
California NeuroAIDS Tissue NetworkU24MH100928 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ACHIM, CRISTIAN L, MOORE, DAVID J · 2013 to 2023
$13.9M
NATIONAL NEUROLOGICAL AIDS BANKU24MH100929 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SINGER, ELYSE J · 2013 to 2023
$12.5M
Texas NeuroAIDS Research CenterU24MH100930 · NIMH · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GELMAN, BENJAMIN B. · 2013 to 2023
$12.1M
NCATS NIH HHS UL1 TR000424NCATS NIH HHS UL1 TR003098NHLBI NIH HHS U01 HL146193NHLBI NIH HHS U01 HL146240NIAID NIH HHS U01 AI035039NIAID NIH HHS U01 AI035040NIAID NIH HHS U01 AI035042NIAID NIH HHS UM1 AI035043NIDA NIH HHS R01 DA040391NIMH NIH HHS U24 MH100925NIMH NIH HHS U24 MH100928NIMH NIH HHS U24 MH100929NIMH NIH HHS U24 MH100930NIMH NIH HHS U24 MH100931
6 · The paper itself

Abstract

backgroundExtracellular vesicles (EVs) are nano-sized particles secreted by most cells. EVs carry nucleic acids that hold promise as potential biomarkers in various diseases. Human immunodeficiency virus type 1 (HIV) infects CD4+ T cells and induces immune dysfunction, inflammation, and EV secretion, but little is known about EV small RNA cargo in relation to immune dysregulation in HIV-infected individuals. Here, we characterize small RNA carried by circulating EVs in HIV-positive subjects on antiretroviral therapy (ART) relative to uninfected controls by next-generation RNA sequencing.

resultsPlasma EVs isolated from HIV-positive and HIV-negative subjects in test (n = 24) and validation (n = 16) cohorts were characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting for exosome markers. EVs were more abundant in plasma from HIV-positive compared to HIV-negative subjects. Small RNA sequencing of plasma EVs in the test cohort identified diverse small RNA species including miRNA, piRNA, snRNA, snoRNA, tRNA, and rRNA, with miRNA being the most abundant. A total of 351 different miRNAs were detected in plasma EVs, with the top 50 miRNAs accounting for 90% of all miRNA reads. miR-26a-5p was the most abundant miRNA, followed by miR-21-5p and miR-148-3p. qRT-PCR analysis showed that six miRNAs (miR-10a-5p, - 21-5p, -27b-3p, - 122-5p, -146a-5p, - 423-5p) were significantly increased in plasma EVs from HIV-positive compared to HIV-negative subjects in the validation cohort. Furthermore, miR-21-5p, -27b-3p, -146a-5p, and - 423-5p correlated positively with metabolite markers of oxidative stress and negatively with anti-inflammatory polyunsaturated fatty acids. Over-representation and pathway enrichment analyses of miRNAs and their target genes predicted functional association with oxidative stress responses, interferon gamma signaling, Toll-like receptor signaling, TGF beta signaling, and Notch signaling.

conclusionsHIV-positive individuals on ART have increased abundance of circulating EVs carrying diverse small RNAs, with miRNAs being the most abundant. Several miRNAs associated with inflammation and oxidative stress are increased in circulating EVs of HIV-positive individuals, representing potential biomarkers of targetable pathways that contribute to disease pathogenesis.

Indexed as

AdultCD4-Positive T-LymphocytesCirculating MicroRNAExtracellular VesiclesFemaleGenetic MarkersHigh-Throughput Nucleotide SequencingHIV-1HIV InfectionsHumansInflammationMaleMiddle AgedOxidative StressCirculating MicroRNAGenetic MarkersExosomesExtracellular vesiclesHIVInflammationMiRNAOxidative stressSmall RNA

Identifiers

PMID33176710
PMCPMC7656686
OpenAlexW3098680894

What OpenQuestion holds

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Registered trials

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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.