Evidence map›Paper›PMID 33690734›Full record

ArticlePLoS pathogens2021

N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages.

Shuliang Chen, Sameer Kumar, Constanza E Espada, Nagaraja Tirumuru, Michael P Cahill, Lulu Hu, Chuan He, Li Wu

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 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

69 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Elevated mBMC cancer · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. High-resolution HIV-1 mNAR genomics and bioinformatics · 2025
    Article
  17. Review
  18. Single-base mJournal of virology · 2025
    Article
  19. Impact of NbioRxiv : the preprint server for biology · 2025
    Article
  20. Article

9 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

8 authors at 4 institutions in 1 country.

Shuliang ChenCenter for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
Sameer KumarDepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Constanza E EspadaDepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0001-7487-5254
Nagaraja TirumuruCenter for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0001-9042-5210
Michael P CahillDepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Lulu HuDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, United States of America.ORCID 0000-0001-7246-1736
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, United States of America.
Li WuDepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.ORCID 0000-0002-5468-2487
University of Iowa · USThe Ohio State University · USHoward Hughes Medical Institute · USUniversity of Chicago · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
Direct Oxidative Nucleic Acids DemethylationR01ES030546 · NIEHS · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2019 to 2023
$1.9M
SAMHD1-mediated regulation of HIV-1 innate immunity and viral gene expressionR01AI141495 · NIAID · UNIVERSITY OF IOWA · PI WU, LI · 2019 to 2023
$1.9M
Mechanisms of HIV-1 RNA Methylation in Regulating Viral ReplicationR01GM128212 · NIGMS · OHIO STATE UNIVERSITY · PI WU, LI · 2017 to 2018
$831k
Mechanisms of HIV-1 RNA Methylation in Regulating Viral ReplicationR01AI150343 · NIAID · UNIVERSITY OF IOWA · PI WU, LI · 2019 to 2020
$768k
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI141495NIAID NIH HHS R01 AI150343NIEHS NIH HHS R01 ES030546NIGMS NIH HHS R01 GM128212
6 · The paper itself

Abstract

N6-methyladenosine (m6A) is a prevalent RNA modification that plays a key role in regulating eukaryotic cellular mRNA functions. RNA m6A modification is regulated by two groups of cellular proteins, writers and erasers that add or remove m6A, respectively. HIV-1 RNA contains m6A modifications that modulate viral infection and gene expression in CD4+ T cells. However, it remains unclear whether m6A modifications of HIV-1 RNA modulate innate immune responses in myeloid cells that are important for antiviral immunity. Here we show that m6A modification of HIV-1 RNA suppresses the expression of antiviral cytokine type-I interferon (IFN-I) in differentiated human monocytic cells and primary monocyte-derived macrophages. Transfection of differentiated monocytic U937 cells with HIV-1 RNA fragments containing a single m6A-modification significantly reduced IFN-I mRNA expression relative to their unmodified RNA counterparts. We generated HIV-1 with altered m6A levels of RNA by manipulating the expression of the m6A erasers (FTO and ALKBH5) or pharmacological inhibition of m6A addition in virus-producing cells, or by treating HIV-1 RNA with recombinant FTO in vitro. HIV-1 RNA transfection or viral infection of differentiated U937 cells and primary macrophages demonstrated that HIV-1 RNA with decreased m6A levels enhanced IFN-I expression, whereas HIV-1 RNA with increased m6A modifications had opposite effects. Our mechanistic studies indicated that m6A of HIV-1 RNA escaped retinoic acid-induced gene I (RIG-I)-mediated RNA sensing and activation of the transcription factors IRF3 and IRF7 that drive IFN-I gene expression. Together, these findings suggest that m6A modifications of HIV-1 RNA evade innate immune sensing in myeloid cells.

Indexed as

AdenosineGene Expression RegulationHIV-1HIV InfectionsHumansImmunity, InnateInterferon Type IMacrophagesMonocytesMyeloid CellsRNA Processing, Post-TranscriptionalRNA, ViralAdenosineInterferon Type IN-methyladenosineRNA, Viral

Identifiers

PMID33690734
PMCPMC7984636
OpenAlexW3135257264

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.