Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production.
Identifieur interne : 001995 ( Main/Exploration ); précédent : 001994; suivant : 001996Altering SARS coronavirus frameshift efficiency affects genomic and subgenomic RNA production.
Auteurs : Ewan P. Plant [États-Unis] ; Amy C. Sims ; Ralph S. Baric ; Jonathan D. Dinman ; Deborah R. TaylorSource :
- Viruses [ 1999-4915 ] ; 2013.
Descripteurs français
- KwdFr :
- ARN viral (génétique), ARN viral (métabolisme), Décalage ribosomique du cadre de lecture, Génome viral, Humains, Mutation avec décalage du cadre de lecture, Protéines virales (génétique), Protéines virales (métabolisme), Réplication virale, Syndrome respiratoire aigu sévère (virologie), Virus du SRAS (génétique), Virus du SRAS (physiologie).
- MESH :
- génétique : ARN viral, Protéines virales, Virus du SRAS.
- métabolisme : ARN viral, Protéines virales.
- physiologie : Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Décalage ribosomique du cadre de lecture, Génome viral, Humains, Mutation avec décalage du cadre de lecture, Réplication virale.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : RNA, Viral, Viral Proteins.
- chemical , metabolism : RNA, Viral, Viral Proteins.
- genetics : SARS Virus.
- physiology : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Frameshift Mutation, Frameshifting, Ribosomal, Genome, Viral, Humans, Virus Replication.
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.
DOI: 10.3390/v5010279
PubMed: 23334702
Affiliations:
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Le document en format XML
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Sims</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author><author><name sortKey="Dinman, Jonathan D" sort="Dinman, Jonathan D" uniqKey="Dinman J" first="Jonathan D" last="Dinman">Jonathan D. Dinman</name></author><author><name sortKey="Taylor, Deborah R" sort="Taylor, Deborah R" uniqKey="Taylor D" first="Deborah R" last="Taylor">Deborah R. 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Plant</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Emerging Pathogens, Division of Transfusion-Transmitted Diseases, Food and Drug Administration, Bethesda, Maryland 20892, USA. Ewan.Plant@fda.hhs.gov</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Emerging Pathogens, Division of Transfusion-Transmitted Diseases, Food and Drug Administration, Bethesda, Maryland 20892</wicri:regionArea><wicri:noRegion>Maryland 20892</wicri:noRegion></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C" last="Sims">Amy C. Sims</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author><author><name sortKey="Dinman, Jonathan D" sort="Dinman, Jonathan D" uniqKey="Dinman J" first="Jonathan D" last="Dinman">Jonathan D. Dinman</name></author><author><name sortKey="Taylor, Deborah R" sort="Taylor, Deborah R" uniqKey="Taylor D" first="Deborah R" last="Taylor">Deborah R. Taylor</name></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Frameshift Mutation</term><term>Frameshifting, Ribosomal</term><term>Genome, Viral</term><term>Humans</term><term>RNA, Viral (genetics)</term><term>RNA, Viral (metabolism)</term><term>SARS Virus (genetics)</term><term>SARS Virus (physiology)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Viral Proteins (genetics)</term><term>Viral Proteins (metabolism)</term><term>Virus Replication</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (génétique)</term><term>ARN viral (métabolisme)</term><term>Décalage ribosomique du cadre de lecture</term><term>Génome viral</term><term>Humains</term><term>Mutation avec décalage du cadre de lecture</term><term>Protéines virales (génétique)</term><term>Protéines virales (métabolisme)</term><term>Réplication virale</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA, Viral</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Viral</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN viral</term><term>Protéines virales</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>ARN viral</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Frameshift Mutation</term><term>Frameshifting, Ribosomal</term><term>Genome, Viral</term><term>Humans</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Décalage ribosomique du cadre de lecture</term><term>Génome viral</term><term>Humains</term><term>Mutation avec décalage du cadre de lecture</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><name sortKey="Dinman, Jonathan D" sort="Dinman, Jonathan D" uniqKey="Dinman J" first="Jonathan D" last="Dinman">Jonathan D. Dinman</name><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C" last="Sims">Amy C. Sims</name><name sortKey="Taylor, Deborah R" sort="Taylor, Deborah R" uniqKey="Taylor D" first="Deborah R" last="Taylor">Deborah R. Taylor</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Plant, Ewan P" sort="Plant, Ewan P" uniqKey="Plant E" first="Ewan P" last="Plant">Ewan P. 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