Evidence map›Paper›PMID 32575413›Full record

ArticleViruses2020

A Low Fidelity Virus Shows Increased Recombination during the Removal of an Alphavirus Reporter Gene.

Tiffany F Kautz, Elizabeth Jaworski, Andrew Routh, Naomi L Forrester

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Can self-amplifying RNA vaccines and viruses exchange genetic material?Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  5. Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  6. Article
  7. Article
  8. 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 2 institutions in 2 countries.

Tiffany F KautzInstitute for Human Infections and Immunity, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.ORCID 0000-0001-7680-4708
Elizabeth JaworskiDepartment of Biochemistry and Molecular Biology, University of Medical Branch, Galveston, TX 77555-0645, USA.ORCID 0000-0002-4886-0451
Andrew RouthDepartment of Biochemistry and Molecular Biology, University of Medical Branch, Galveston, TX 77555-0645, USA.ORCID 0000-0002-2874-5990
Naomi L ForresterInstitute for Human Infections and Immunity, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
The University of Texas Medical Branch at Galveston · USThe University of Texas Health Science Center at San Antonio · US

Funding

EMERGING AND TROPICAL INFECTIOUS DISEASEST32AI007526 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI SOONG, LYNN · 1997 to 2025
$3.1M
Engineering high fidelity mutations to increase safety of live-attenuated alphavirus vaccinesR01AI125902 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI COFFEY, LARK L · 2016 to 2020
$2.6M
NIAID NIH HHS R01 AI125902NIH HHS R01-AI095753-01A1NIH HHS R01-AI125902-01NIH HHS T32 AI007526
6 · The paper itself

Abstract

Reporter genes for RNA viruses are well-known to be unstable due to putative RNA recombination events that excise inserted nucleic acids. RNA recombination has been demonstrated to be co-regulated with replication fidelity in alphaviruses, but it is unknown how recombination events at the minority variant level act, which is important for vaccine and trans-gene delivery design. Therefore, we sought to characterize the removal of a reporter gene by a low-fidelity alphavirus mutant over multiple replication cycles. To examine this, GFP was inserted into TC-83, a live-attenuated vaccine for the alphavirus Venezuelan equine encephalitis virus, as well as a low-fidelity variant of TC-83, and passaged until fluorescence was no longer observed. Short-read RNA sequencing using ClickSeq was performed to determine which regions of the viral genome underwent recombination and how this changed over multiple replication cycles. A rapid removal of the GFP gene was observed, where minority variants in the virus population accumulated small deletions that increased in size over the course of passaging. Eventually, these small deletions merged to fully remove the GFP gene. The removal was significantly enhanced during the passaging of low-fidelity TC-83, suggesting that increased levels of recombination are a defining characteristic of this mutant.

Indexed as

Gene DeletionAnimalsCell LineChlorocebus aethiopsClick ChemistryEncephalitis Virus, Venezuelan EquineGenes, ReporterGenome, ViralGreen Fluorescent ProteinsHorsesRecombination, GeneticRNARNA, ViralSequence Analysis, RNAVaccines, AttenuatedVero CellsGreen Fluorescent ProteinsRNARNA, recombinantRNA, ViralVaccines, Attenuatedalphavirusarbovirusfidelityrecombinationsequencing

Identifiers

PMID32575413
PMCPMC7354468
OpenAlexW3036571940

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.