Evidence map›Paper›PMID 28738877›Full record

ArticleVirology journal2017

Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA.

Bo Meng, Kirsten Bentley, Anthony C Marriott, Paul D Scott, Nigel J Dimmock, Andrew J Easton

Abstract read
In one paragraph

Article in Virology journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

18 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

6 authors.

Bo MengPresent Address: Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
Kirsten BentleyPresent Address: Biomedical Sciences Research Complex, North Haugh, University of St. Andrews, St Andrews, KY16 9ST, UK.
Anthony C MarriottPresent Address: Public Health England, Porton Down, Salisbury, SP4 0JG, UK.
Paul D ScottPresent Address: Public Health England Birmingham Microbiology, Department of Pathology, Heart of England NHS Foundation Trust, Heartlands Hospital, Bordesley Green East, Salisbury, B9 5SS, UK.
Nigel J DimmockSchool of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK.
Andrew J EastonSchool of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK. a.j.easton@warwick.ac.uk.

Funding

Medical Research Council G0600832
6 · The paper itself

Abstract

backgroundDefective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I.

resultsWe have investigated the RNA inhibitory mechanism(s) of DI 1/244 RNA. Ablation of initiation codons does not diminish interference showing that no protein product is required for protection. Further analysis indicated that 1/244 DI RNA interferes by replacing the cognate full-length segment 1 RNA in progeny virions, while interfering with the expression of genome segment 1, its cognate RNA, and genome RNAs 2 and 3, but not genome RNA 6, a representative of the non-polymerase genes.

conclusionsOur data contradict the dogma that a DI RNA only interferes with expression from its cognate full-length segment. There is reciprocity as cloned segment 2 and 3 DI RNAs inhibited expression of RNAs from a segment 1 target. These data demonstrate an unexpected complexity in the mechanism of interference by this cloned therapeutic DI RNA.

Indexed as

Defective VirusesHEK293 CellsHumansInfluenza A virusInterferon Type IRNA InterferenceRNA, ViralInterferon Type IRNA, ViralDefective interfering RNAInfluenza virusInterferenceReplication

Identifiers

PMID28738877
PMCPMC5525295

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.