Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome.
Identifieur interne : 003D42 ( Main/Exploration ); précédent : 003D41; suivant : 003D43Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome.
Auteurs : Boyd Yount [États-Unis] ; Rhonda S. Roberts ; Lisa Lindesmith ; Ralph S. BaricSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2006.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- genetics : SARS Virus.
- metabolism : SARS Virus.
- Animals, Base Sequence, Gene Expression Regulation, Viral, Genome, Humans, Molecular Sequence Data, Open Reading Frames, Recombination, Genetic, Transcription, Genetic.
Abstract
Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses.
DOI: 10.1073/pnas.0605438103
PubMed: 16891412
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 002138
- to stream PubMed, to step Curation: 002138
- to stream PubMed, to step Checkpoint: 002032
- to stream Ncbi, to step Merge: 001608
- to stream Ncbi, to step Curation: 001608
- to stream Ncbi, to step Checkpoint: 001608
- to stream Main, to step Merge: 003F15
- to stream Main, to step Curation: 003D42
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome.</title><author><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name><affiliation wicri:level="2"><nlm:affiliation>Department of Epidemiology, Program in Infectious Diseases, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Program in Infectious Diseases, School of Public Health, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Roberts, Rhonda S" sort="Roberts, Rhonda S" uniqKey="Roberts R" first="Rhonda S" last="Roberts">Rhonda S. Roberts</name></author><author><name sortKey="Lindesmith, Lisa" sort="Lindesmith, Lisa" uniqKey="Lindesmith L" first="Lisa" last="Lindesmith">Lisa Lindesmith</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></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16891412</idno><idno type="pmid">16891412</idno><idno type="doi">10.1073/pnas.0605438103</idno><idno type="wicri:Area/PubMed/Corpus">002138</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002138</idno><idno type="wicri:Area/PubMed/Curation">002138</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002138</idno><idno type="wicri:Area/PubMed/Checkpoint">002032</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002032</idno><idno type="wicri:Area/Ncbi/Merge">001608</idno><idno type="wicri:Area/Ncbi/Curation">001608</idno><idno type="wicri:Area/Ncbi/Checkpoint">001608</idno><idno type="wicri:doubleKey">0027-8424:2006:Yount B:rewiring:the:severe</idno><idno type="wicri:Area/Main/Merge">003F15</idno><idno type="wicri:Area/Main/Curation">003D42</idno><idno type="wicri:Area/Main/Exploration">003D42</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome.</title><author><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name><affiliation wicri:level="2"><nlm:affiliation>Department of Epidemiology, Program in Infectious Diseases, School of Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Program in Infectious Diseases, School of Public Health, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Roberts, Rhonda S" sort="Roberts, Rhonda S" uniqKey="Roberts R" first="Rhonda S" last="Roberts">Rhonda S. Roberts</name></author><author><name sortKey="Lindesmith, Lisa" sort="Lindesmith, Lisa" uniqKey="Lindesmith L" first="Lisa" last="Lindesmith">Lisa Lindesmith</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></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Gene Expression Regulation, Viral</term><term>Genome</term><term>Humans</term><term>Molecular Sequence Data</term><term>Open Reading Frames</term><term>Recombination, Genetic</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Transcription, Genetic</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cadres ouverts de lecture</term><term>Données de séquences moléculaires</term><term>Génome</term><term>Humains</term><term>Recombinaison génétique</term><term>Régulation de l'expression des gènes viraux</term><term>Séquence nucléotidique</term><term>Transcription génétique</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Base Sequence</term><term>Gene Expression Regulation, Viral</term><term>Genome</term><term>Humans</term><term>Molecular Sequence Data</term><term>Open Reading Frames</term><term>Recombination, Genetic</term><term>Transcription, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cadres ouverts de lecture</term><term>Données de séquences moléculaires</term><term>Génome</term><term>Humains</term><term>Recombinaison génétique</term><term>Régulation de l'expression des gènes viraux</term><term>Séquence nucléotidique</term><term>Transcription génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Live virus vaccines provide significant protection against many detrimental human and animal diseases, but reversion to virulence by mutation and recombination has reduced appeal. Using severe acute respiratory syndrome coronavirus as a model, we engineered a different transcription regulatory circuit and isolated recombinant viruses. The transcription network allowed for efficient expression of the viral transcripts and proteins, and the recombinant viruses replicated to WT levels. Recombinant genomes were then constructed that contained mixtures of the WT and mutant regulatory circuits, reflecting recombinant viruses that might occur in nature. Although viable viruses could readily be isolated from WT and recombinant genomes containing homogeneous transcription circuits, chimeras that contained mixed regulatory networks were invariantly lethal, because viable chimeric viruses were not isolated. Mechanistically, mixed regulatory circuits promoted inefficient subgenomic transcription from inappropriate start sites, resulting in truncated ORFs and effectively minimize viral structural protein expression. Engineering regulatory transcription circuits of intercommunicating alleles successfully introduces genetic traps into a viral genome that are lethal in RNA recombinant progeny viruses.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region></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="Lindesmith, Lisa" sort="Lindesmith, Lisa" uniqKey="Lindesmith L" first="Lisa" last="Lindesmith">Lisa Lindesmith</name><name sortKey="Roberts, Rhonda S" sort="Roberts, Rhonda S" uniqKey="Roberts R" first="Rhonda S" last="Roberts">Rhonda S. Roberts</name></noCountry><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003D42 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 003D42 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:16891412
|texte= Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:16891412" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |