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U.S. Department of Health and Human Services

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Viruses 2013 Jan 18;5(1):279-94

Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production.

Plant EP, Sims AC, Baric RS, Dinman JD, Taylor DR


In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID50 suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication.

Category: Journal Article
PubMed ID: #23334702 DOI: 10.3390/v5010279
PubMed Central ID: #PMC3564121
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2012-08-24 Entry Last Modified: 2013-04-28