title: Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production.
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.
authors: Laboratory of Emerging Pathogens, Division of Transfusion-Transmitted Diseases, Food and Drug Administration, Bethesda, Maryland 20892, USA. Ewan.Plant@fda.hhs.gov
authors: Ewan P
authors: EP
authors: Plant
authors: Amy C
authors: AC
authors: Sims
authors: Ralph S
authors: RS
authors: Baric
authors: Jonathan D
authors: JD
authors: Dinman
authors: Deborah R
authors: DR
authors: Taylor
mesh_terms: D016368:Frameshift Mutation; D018965:Frameshifting, Ribosomal; D016679:Genome, Viral; D006801:Humans; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins