Evidence map›Paper›PMID 30995283›Full record

ArticlePLoS pathogens2019

A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes.

Yan Sun, Eun Ji Kim, Sébastien A Felt, Louis J Taylor, Divyansh Agarwal, Gregory R Grant, Carolina B López

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 56 citations in OpenAlex.

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  18. Introduction to Respiratory Syncytial Virus.Methods in molecular biology (Clifton, N.J.) · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yan SunDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.ORCID 0000-0002-5320-5793
Eun Ji KimInstitute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Sébastien A FeltDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Louis J TaylorDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.ORCID 0000-0002-6993-5838
Divyansh AgarwalDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Gregory R GrantInstitute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Carolina B LópezDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States.
University of Pennsylvania · USTranslational Therapeutics (United States) · US

Funding

TRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8M
Defective Viral genomes in RSV pathogenesisR01AI137062 · NIAID · WASHINGTON UNIVERSITY · PI Carolina B. Lopez · 2018 to 2026
$4.2M
A novel virus-derived adjuvantR01AI083284 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LOPEZ, CAROLINA B. · 2009 to 2017
$3.3M
NIAID NIH HHS R01 AI083284NIAID NIH HHS R01 AI137062NIAID NIH HHS T32 AI007324
6 · The paper itself

Abstract

Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence. The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process. These findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.

Indexed as

Genome, ViralVirus ReplicationA549 CellsAntiviral AgentsChildDefective VirusesGene Expression Regulation, ViralHeLa CellsHigh-Throughput Nucleotide SequencingHumansMutationNasopharyngeal NeoplasmsRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsRNA, ViralTranscription, GeneticAntiviral AgentsRNA, ViralViral Proteins

Identifiers

PMID30995283
PMCPMC6504078
OpenAlexW2936162970

What OpenQuestion holds

Textmetadata
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.