Evidence map›Paper›PMID 29942657›Full record

ArticleVirus evolution2018

Viral attenuation by engineered protein fragmentation.

Daniel J Garry, Andrew D Ellington, Ian J Molineux, James J Bull

Open access · goldAbstract read
In one paragraph

Article in Virus evolution, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 40% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

4 authors at 1 institution in 1 country.

Daniel J GarryDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, TX 78712, USA.
Andrew D EllingtonDepartment of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas, Austin, TX 78712, USA.
Ian J MolineuxDepartment of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA.
James J BullDepartment of Integrative Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA.
The University of Texas at Austin · US

Funding

Sequence-structure-function relationships in human visual photopigmentsP20GM104420 · NIGMS · UNIVERSITY OF IDAHO · PI WICHMAN, HOLLY A · 2015 to 2024
$22.9M
Genomics Resources Core (GRC)P30GM103324 · NIGMS · UNIVERSITY OF IDAHO · PI FORNEY, LARRY J · 2013 to 2017
$5.0M
The biophysical basis of translational selectionR01GM088344 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BARRICK, JEFFREY EVAN, WILKE, CLAUS O · 2009 to 2023
$3.5M
Identifying Mutations that Promote Microbial EvolvabilityK99GM087550 · NIGMS · MICHIGAN STATE UNIVERSITY · PI BARRICK, JEFFREY EVAN · 2009 to 2010
$180k
NIGMS NIH HHS K99 GM087550NIGMS NIH HHS P20 GM104420NIGMS NIH HHS P30 GM103324NIGMS NIH HHS R01 GM088344
6 · The paper itself

Abstract

A possible but untested method of viral attenuation is protein fragmentation, engineering wild-type proteins as two or more peptides that self-assemble after translation. Here, the bacteriophage T7 was engineered to encode its essential RNA polymerase as two peptides. Initial fitness was profoundly suppressed. Subjecting the engineered virus to over 100 generations of adaptation by serial transfer resulted in a large fitness increase, still remaining below that of evolved wild-type. The fitness increase was accompanied by three substitutions in the fragmented peptides as well as six mutations in other parts of the genome, but the fragmentation was retained. This study thereby demonstrates the feasibility of using gene fragmentation as a possibly permanent method of attenuation, but the initial fitness of the engineered genome may be a poor measure of its fitness on extended adaptation.

Indexed as

adaptationattenuationbacteriophageevolutiongenome engineering

Identifiers

PMID29942657
PMCPMC6009699
OpenAlexW2809427642

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.