Evidence map›Paper›PMID 30962389›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Ebolavirus polymerase uses an unconventional genome replication mechanism.

Laure R Deflubé, Tessa N Cressey, Adam J Hume, Judith Olejnik, Elaine Haddock, Friederike Feldmann, Hideki Ebihara, Rachel Fearns, Elke Mühlberger

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–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

23 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Laure R DeflubéDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118.
Tessa N CresseyDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118.
Adam J HumeDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118.
Judith OlejnikDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118.
Elaine HaddockRocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Friederike FeldmannRocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840.
Hideki EbiharaDepartment of Molecular Medicine, Mayo Clinic, Rochester, MN 55905.
Rachel FearnsDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118; rfearns@bu.edu muehlber@bu.edu.
Elke MühlbergerDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118; rfearns@bu.edu muehlber@bu.edu.ORCID 0000-0003-3547-9376

Funding

Mechanisms of Marburg virus gene expressionR01AI133486 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FEARNS, RACHEL, MUHLBERGER, ELKE C · 2018 to 2022
$2.7M
Initiation and regulation of RSV mRNA transcription and genome replicationR01AI113321 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FEARNS, RACHEL · 2014 to 2017
$1.7M
Antiviral responses in iPSC-derived human primary cells to Ebola virus infectionR21AI126457 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MOSTOSLAVSKY, GUSTAVO, MUHLBERGER, ELKE C · 2016 to 2017
$480k
Filovirus replication: initiation mechanism and role of RNA secondary structuresR03AI114293 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MUHLBERGER, ELKE C · 2014 to 2015
$164k
NIAID NIH HHS R01 AI113321NIAID NIH HHS R01 AI133486NIAID NIH HHS R03 AI114293NIAID NIH HHS R21 AI126457
6 · The paper itself

Abstract

Most nonsegmented negative strand (NNS) RNA virus genomes have complementary 3' and 5' terminal nucleotides because the promoters at the 3' ends of the genomes and antigenomes are almost identical to each other. However, according to published sequences, both ends of ebolavirus genomes show a high degree of variability, and the 3' and 5' terminal nucleotides are not complementary. If correct, this would distinguish the ebolaviruses from other NNS RNA viruses. Therefore, we investigated the terminal genomic and antigenomic nucleotides of three different ebolavirus species, Ebola (EBOV), Sudan, and Reston viruses. Whereas the 5' ends of ebolavirus RNAs are highly conserved with the sequence ACAGG-5', the 3' termini are variable and are typically 3'-GCCUGU, ACCUGU, or CCUGU. A small fraction of analyzed RNAs had extended 3' ends. The majority of 3' terminal sequences are consistent with a mechanism of nucleotide addition by hairpin formation and back-priming. Using single-round replicating EBOV minigenomes, we investigated the effect of the 3' terminal nucleotide on viral replication and found that the EBOV polymerase initiates replication opposite the 3'-CCUGU motif regardless of the identity of the 3' terminal nucleotide(s) and of the position of this motif relative to the 3' end. Deletion or mutation of the first residue of the 3'-CCUGU motif completely abolished replication initiation, suggesting a crucial role of this nucleotide in directing initiation. Together, our data show that ebolaviruses have evolved a unique replication strategy among NNS RNA viruses resulting in 3' overhangs. This could be a mechanism to avoid antiviral recognition.

Indexed as

EbolavirusRNA, ViralBase SequenceGenome, ViralNucleotidesVirus ReplicationNucleotidesRNA, ViralEbola virus genome endsEbola virus replicationebolavirus replication initiationnonsegmented negative strand RNA virus replicationvariable 3′ genome ends

Identifiers

PMID30962389
PMCPMC6486738

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.