Evidence map›Paper›PMID 21068252›Full record

ArticleJournal of virology2011

Rabies virus (RV) glycoprotein expression levels are not critical for pathogenicity of RV.

Christoph Wirblich, Matthias J Schnell

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
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  3. "Self-inactivating" rabies viruses are susceptible to loss of their intended attenuating modification.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  19. Phenotypic ConsequencesFrontiers in microbiology · 2017
    Article
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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

2 authors at 1 institution in 1 country.

Christoph WirblichDepartment of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
Matthias J Schnell
Thomas Jefferson University · US

Funding

CENTER FOR NEUROANATOMY WITH NEUROTROPIC VIRUSES: COMPARATIVE MEDICINEP40RR018604 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STRICK, PETER · 2004 to 2011
$6.5M
Functional Analysis of NSV-based HIV vectorsP01AI082325 · NIAID · THOMAS JEFFERSON UNIVERSITY · PI SCHNELL, MATTHIAS JOHANNES · 2009 to 2010
$2.7M
NCRR NIH HHS P40 RR018604NCRR NIH HHS P40RR018604NIAID NIH HHS AI082325NIAID NIH HHS P01 AI082325
6 · The paper itself

Abstract

Previous comparisons of different rabies virus (RV) strains suggested an inverse relationship between pathogenicity and the amount of glycoprotein produced in infected cells. In order to provide more insight into this relationship, we pursued an experimental approach that allowed us to alter the glycoprotein expression level without altering the glycoprotein sequence, thereby eliminating the contribution of amino acid changes to differences in viral virulence. To this end, we constructed an infectious clone of the highly pathogenic rabies virus strain CVS-N2c and replaced its cognate glycoprotein gene with synthetic versions in which silent mutations were introduced to replace wild-type codons with the most or least frequently used synonymous codons. A recombinant N2c variant containing the fully codon-optimized G gene and three variants carrying a partially codon-deoptimized G gene were recovered on mouse neuroblastoma cells and shown to express 2- to 3-fold more and less glycoprotein, respectively, than wild-type N2c. Pathogenicity studies in mice revealed the WT-N2c virus to be the most pathogenic strain. Variants containing partially codon-deoptimized glycoprotein genes or the codon-optimized gene were less pathogenic than WT-N2c but still caused significant mortality. We conclude that the expression level of the glycoprotein gene does have an impact on pathogenicity but is not a dominant factor that determines pathogenicity. Thus, strategies such as changes in codon usage that aim solely at altering the expression level of the glycoprotein gene do not suffice to render a pathogenic rabies virus apathogenic and are not a viable and safe approach for attenuation of a pathogenic strain.

Indexed as

Gene ExpressionAnimalsAntigens, ViralCell LineCodonDisease Models, AnimalGlycoproteinsMaleMiceMolecular Sequence DataNeuronsRabiesRabies virusSequence Analysis, DNASurvival AnalysisViral Envelope ProteinsAntigens, ViralCodonglycoprotein G, Rabies virusGlycoproteinsViral Envelope Proteins

Identifiers

PMID21068252
PMCPMC3020019
OpenAlexW2092342786

What OpenQuestion holds

Textmetadata
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.