Evidence map›Paper›PMID 34929018›Full record

ArticlePLoS pathogens2021

Viral RNA N6-methyladenosine modification modulates both innate and adaptive immune responses of human respiratory syncytial virus.

Miaoge Xue, Yuexiu Zhang, Haitao Wang, Elizabeth L Kairis, Mijia Lu, Sadeem Ahmad, Zayed Attia, Olivia Harder, Zijie Zhang, Jiangbo Wei and 9 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.3field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Article
  3. Hypoxia inducible factors regulate pneumovirus replication by enhancing innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  4. Review
  5. mFrontiers in immunology · 2026
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  9. RNA mCell investigation · 2025
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  12. Proceedings of the National Academy of Sciences of the United States of America · 2025
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  13. Article
  14. Review
  15. Article
  16. Epitranscriptomic mScience advances · 2024
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  17. Recent insights into NCurrent opinion in genetics & development · 2024
    Review
  18. mViruses · 2024
    Article
  19. Challenges to mapping and defining mRNA (New York, N.Y.) · 2024
    Article
  20. mViruses · 2024
    Review
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

19 authors at 4 institutions in 1 country.

Miaoge XueDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Yuexiu ZhangDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Haitao WangDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
Elizabeth L KairisDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Mijia LuDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0002-4438-980X
Sadeem AhmadDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
Zayed AttiaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0001-6930-8343
Olivia HarderDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0002-5420-0134
Zijie ZhangDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America.
Jiangbo WeiDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, United States of America.
Phylip ChenCenter for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Youling GaoDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Mark E PeeplesCenter for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.ORCID 0000-0002-4582-317X
Amit SharmaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Prosper BoyakaDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.
Chuan HeProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Sun HurDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0001-5005-5550
Stefan NiewieskDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0003-4487-073X
Jianrong LiDepartment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America.ORCID 0000-0002-7130-1084
The Ohio State University · USBoston Children's Hospital · USNationwide Children's Hospital · USUniversity of Chicago · US

Funding

Transcriptome-wide base-resolution sequencing of pseudouridine in human normal and AD brain tissues-CEGS Admin supplement 2020-2021RM1HG008935 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2016 to 2025
$24.4M
Project 3: Dr. LiP01AI112524 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI LI, JIANRONG · 2015 to 2019
$6.8M
Structural and functional analyses of the RIG-I filament in innate immunityR01AI111784 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI HUR, SUN · 2014 to 2023
$4.9M
Messenger RNA Capping and Methylation in PneumovirusesR01AI090060 · NIAID · OHIO STATE UNIVERSITY · PI LI, JIANRONG · 2011 to 2023
$4.0M
Host innate immune response as a barrier to cross-species retrovirus transmissionR00AI125136 · NIAID · OHIO STATE UNIVERSITY · PI SHARMA, AMIT · 2019 to 2020
$498k
Messenger RNA capping and methylation in pneumovirusesR56AI090060 · NIAID · OHIO STATE UNIVERSITY · PI LI, JIANRONG, NIEWIESK, STEFAN · 2010 to 2010
$373k
NHGRI NIH HHS RM1 HG008935NIAID NIH HHS P01 AI112524NIAID NIH HHS R00 AI125136NIAID NIH HHS R01 AI090060NIAID NIH HHS R01 AI111784NIAID NIH HHS R56 AI090060
6 · The paper itself

Abstract

Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in humans. A well-known challenge in the development of a live attenuated RSV vaccine is that interferon (IFN)-mediated antiviral responses are strongly suppressed by RSV nonstructural proteins which, in turn, dampens the subsequent adaptive immune responses. Here, we discovered a novel strategy to enhance innate and adaptive immunity to RSV infection. Specifically, we found that recombinant RSVs deficient in viral RNA N6-methyladenosine (m6A) and RSV grown in m6A methyltransferase (METTL3)-knockdown cells induce higher expression of RIG-I, bind more efficiently to RIG-I, and enhance RIG-I ubiquitination and IRF3 phosphorylation compared to wild-type virion RNA, leading to enhanced type I IFN production. Importantly, these m6A-deficient RSV mutants also induce a stronger IFN response in vivo, are significantly attenuated, induce higher neutralizing antibody and T cell immune responses in mice and provide complete protection against RSV challenge in cotton rats. Collectively, our results demonstrate that inhibition of RSV RNA m6A methylation enhances innate immune responses which in turn promote adaptive immunity.

Indexed as

RNA, ViralAdaptive ImmunityAdenosineAnimalsImmunity, InnateMethylationMiceRatsRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsAdenosineN-methyladenosineRNA, Viral

Identifiers

PMID34929018
PMCPMC8759664
OpenAlexW4200044314

What OpenQuestion holds

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LicenceCC BY
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.