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Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production

Ewan P Plant1, Amy C Sims, Ralph S Baric

  • 1Laboratory of Emerging Pathogens, Division of Transfusion-Transmitted Diseases, Food and Drug Administration, Bethesda, Maryland 20892, USA. Ewan.Plant@fda.hhs.gov

Viruses
|January 22, 2013
PubMed

Insights

Synonymous codon changes in coronaviruses alter RNA production by affecting programmed ribosomal frameshifting efficiency. This suggests RNA sequence, not protein sequence, critically impacts viral replication and optimal virus yield.

Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Coronaviruses exhibit variations in genomic and subgenomic RNA production linked to mutations in the programmed ribosomal frameshift signal.
  • Previous studies could not definitively attribute these variations to genomic sequence, protein sequence, or frameshifting frequency.

Purpose of the Study:

  • To investigate the impact of synonymous codon changes on coronavirus RNA production.
  • To determine whether protein sequence or RNA sequence/frameshifting efficiency is the primary driver of altered RNA ratios.

Main Methods:

  • Engineered coronaviruses with synonymous codon changes within the programmed ribosomal frameshift signal.
  • Quantified genomic and subgenomic RNA ratios.
  • Assessed frameshifting efficiency and viral titers (TCID50).

Main Results:

  • Synonymous codon changes led to altered genomic and subgenomic RNA ratios.
  • These changes were attributed to modifications in the frameshift signal structure and efficiency, not the resulting protein sequence.
  • Minor variations in frameshifting efficiency caused significant changes in genomic RNA production and viral titer (TCID50).

Conclusions:

  • The RNA sequence, specifically through its influence on frameshifting efficiency, is the primary determinant of altered genomic and subgenomic RNA production in coronaviruses.
  • A minimum frameshifting frequency threshold is crucial for optimal virus production.
  • Either the RNA sequence itself or the resulting viral protein ratios from varying frameshifting levels influence viral replication.

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