Evidence map›Paper›PMID 16973573›Full record

ArticleJournal of virology2006

Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimization causes attenuation of viral virulence by lowering specific infectivity.

Steffen Mueller, Dimitris Papamichail, J Robert Coleman, Steven Skiena, Eckard Wimmer

Abstract read
In one paragraph

Article in Journal of virology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers.

0numbers the graph read from it
0cells of the map it votes in
219citing 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

219 citing papers in PubMed.

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  14. tRNA Modifications: A Tale of Two Viruses-SARS-CoV-2 and ZIKV.International journal of molecular sciences · 2025
    Article
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  16. Review
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159 more citing papers are in PubMed but not listed here.

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

5 authors.

Steffen MuellerDepartment of Molecular Genetics and Microbiology, Life Sciences Building, Stony Brook University, Stony Brook, NY 11794-5222, USA. smueller@ms.cc.sunysb.edu
Dimitris Papamichail
J Robert Coleman
Steven Skiena
Eckard Wimmer

Funding

VIRAL ONCOLOGYT32CA009176 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HEARING, PATRICK · 1985 to 2012
$5.2M
POLIOVIRUS--MOLECULAR BIOLOGY AND SURFACE STRUCTURER37AI015122 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI WIMMER, ECKARD · 1988 to 2007
$3.8M
POLIOVIRUS MOLECULAR BIOLOGY AND SURFACE STRUCTURER01AI015122 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI WIMMER, ECKARD · 1985 to 2013
$1.9M
NCI NIH HHS T32 CA009176NCI NIH HHS T32-CA009176NIAID NIH HHS AI15122NIAID NIH HHS R01 AI015122NIAID NIH HHS R37 AI015122
6 · The paper itself

Abstract

Exploring the utility of de novo gene synthesis with the aim of designing stably attenuated polioviruses (PV), we followed two strategies to construct PV variants containing synthetic replacements of the capsid coding sequences either by deoptimizing synonymous codon usage (PV-AB) or by maximizing synonymous codon position changes of the existing wild-type (wt) poliovirus codons (PV-SD). Despite 934 nucleotide changes in the capsid coding region, PV-SD RNA produced virus with wild-type characteristics. In contrast, no viable virus was recovered from PV-AB RNA carrying 680 silent mutations, due to a reduction of genome translation and replication below a critical level. After subcloning of smaller portions of the AB capsid coding sequence into the wt background, several viable viruses were obtained with a wide range of phenotypes corresponding to their efficiency of directing genome translation. Surprisingly, when inoculated with equal infectious doses (PFU), even the most replication-deficient viruses appeared to be as pathogenic in PV-sensitive CD155tg (transgenic) mice as the PV(M) wild type. However, infection with equal amounts of virus particles revealed a neuroattenuated phenotype over 100-fold. Direct analysis indicated a striking reduction of the specific infectivity of PV-AB-type virus particles. Due to the distribution effect of many silent mutations over large genome segments, codon-deoptimized viruses should have genetically stable phenotypes, and they may prove suitable as attenuated substrates for the production of poliovirus vaccines.

Indexed as

AnimalsCapsid ProteinsCodonEnzyme-Linked Immunosorbent AssayGenome, ViralHeLa CellsHumansMembrane ProteinsMiceMice, TransgenicPhenotypePoliomyelitisPoliovirusProtein BiosynthesisReceptors, VirusVirulenceCapsid ProteinsCodonMembrane Proteinspoliovirus receptorReceptors, Virus

Identifiers

PMID16973573
PMCPMC1617239

What OpenQuestion holds

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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.