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Viruses 2013, 5(1), 279-294; doi:10.3390/v5010279
Article

Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production

1,†
,
2
,
2,3
,
4
 and
1,*
1 Laboratory of Emerging Pathogens, Division of Transfusion-Transmitted Diseases, Food and Drug Administration, Bethesda, Maryland 20892, USA 2 Departments of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA 3 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599, USA 4 Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA Current address: Division of Viral Products, Food and Drug Administration, Bethesda, Maryland 20892, USA.
* Author to whom correspondence should be addressed.
Received: 6 December 2012 / Revised: 14 January 2013 / Accepted: 15 January 2013 / Published: 18 January 2013
(This article belongs to the Special Issue Animal Arteriviruses and Coronaviruses)
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Abstract

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.
Keywords: SARS; severe acute respiratory syndrome; pseudoknot; ribosomal frameshifting; viral replication SARS; severe acute respiratory syndrome; pseudoknot; ribosomal frameshifting; viral replication
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Plant, E.P.; Sims, A.C.; Baric, R.S.; Dinman, J.D.; Taylor, D.R. Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production. Viruses 2013, 5, 279-294.

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