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July 16, 2009Journal of VirologyOpen Access

Genetic Inactivation of Poliovirus Infectivity by Increasing the Frequencies of CpG and UpA Dinucleotides within and across Synonymous Capsid Region Codons

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Population

Poliovirus type 2 prototype strain MEF-1 infectious clone cultured in HeLa and RD cells

Comparison

Synonymous codon replacements in the capsid… vs Unmodified wild-type MEF-1 reference construct

Design

Preclinical

Authors

CBCara C. BurnsCenters for Disease Control and PreventionRCRaymond P. CampagnoliOak Ridge Associated UniversitiesJSJing ShawCenters for Disease Control and Prevention

Discussion

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Implication

Hypothesis-generating for stable poliovirus attenuation via dinucleotide saturation; prospective human studies needed before clinical use.

Structured PICO

P
Population
Poliovirus type 2 prototype strain MEF-1 infectious clone cultured in HeLa and RD cells
I
Intervention
Synonymous codon replacements in the capsid coding region to increase frequencies of CpG and UpA dinucleotides
C
Comparator
Unmodified wild-type MEF-1 reference construct (ABC)
O
Outcome
Replicative fitness measured by plaque areas and virus yields in single-step growth experimentssurrogate

Increasing the frequencies of CpG and UpA dinucleotides via synonymous codon replacement offers a general approach to developing attenuated vaccines with high genetic stability.

Cite This Study

Burns et al. (2009) studied this question.

synapsesocial.com/papers/6a71f2892163a0a01bc5dcd4https://doi.org/10.1128/jvi.00508-09
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.1992 · 82 citations
  2. 2Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region2006 · 265 citations
  3. 3Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine1995 · 140 citations
  4. 4A mutation in the RNA polymerase of poliovirus type 1 contributes to attenuation in mice1993 · 64 citations
  5. 5Serial Recombination during Circulation of Type 1 Wild-Vaccine Recombinant Polioviruses in China2003 · 88 citations