One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities
Identifieur interne : 001607 ( Main/Exploration ); précédent : 001606; suivant : 001608One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities
Auteurs : Lorenzo Subissi [France] ; Clara C. Posthuma [Pays-Bas] ; Axelle Collet [France] ; Jessika C. Zevenhoven-Dobbe [Pays-Bas] ; Alexander E. Gorbalenya [Pays-Bas, Russie] ; Etienne Decroly [France] ; Eric J. Snijder [Pays-Bas] ; Bruno Canard [France] ; Isabelle Imbert [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Descripteurs français
- KwdFr :
- ARN (métabolisme), ARN viral (biosynthèse), Biocatalyse, Complexes multiprotéiques (métabolisme), DNA-directed RNA polymerases (métabolisme), Données de séquences moléculaires, Exoribonucleases (métabolisme), Génétique inverse, Humains, Liaison aux protéines, Mutation (génétique), Protéines mutantes (métabolisme), Protéines virales non structurales (métabolisme), Reproductibilité des résultats, Réplication virale, Syndrome respiratoire aigu sévère (virologie), Séquence nucléotidique, Virus du SRAS (métabolisme).
- MESH :
- biosynthèse : ARN viral.
- génétique : Mutation.
- métabolisme : ARN, Complexes multiprotéiques, DNA-directed RNA polymerases, Exoribonucleases, Protéines mutantes, Protéines virales non structurales, Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Biocatalyse, Données de séquences moléculaires, Génétique inverse, Humains, Liaison aux protéines, Reproductibilité des résultats, Réplication virale, Séquence nucléotidique.
English descriptors
- KwdEn :
- Base Sequence, Biocatalysis, DNA-Directed RNA Polymerases (metabolism), Exoribonucleases (metabolism), Humans, Molecular Sequence Data, Multiprotein Complexes (metabolism), Mutant Proteins (metabolism), Mutation (genetics), Protein Binding, RNA (metabolism), RNA, Viral (biosynthesis), Reproducibility of Results, Reverse Genetics, SARS Virus (metabolism), Severe Acute Respiratory Syndrome (virology), Viral Nonstructural Proteins (metabolism), Virus Replication.
- MESH :
- chemical , biosynthesis : RNA, Viral.
- chemical , metabolism : DNA-Directed RNA Polymerases, Exoribonucleases, Multiprotein Complexes, Mutant Proteins, RNA, Viral Nonstructural Proteins.
- genetics : Mutation.
- metabolism : SARS Virus.
- virology : Severe Acute Respiratory Syndrome.
- Base Sequence, Biocatalysis, Humans, Molecular Sequence Data, Protein Binding, Reproducibility of Results, Reverse Genetics, Virus Replication.
Abstract
The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.
Url:
DOI: 10.1073/pnas.1323705111
PubMed: 25197083
PubMed Central: 4169972
Affiliations:
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<term>Exoribonucleases (metabolism)</term>
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<term>Molecular Sequence Data</term>
<term>Multiprotein Complexes (metabolism)</term>
<term>Mutant Proteins (metabolism)</term>
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<term>RNA, Viral (biosynthesis)</term>
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<term>Severe Acute Respiratory Syndrome (virology)</term>
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<term>Complexes multiprotéiques (métabolisme)</term>
<term>DNA-directed RNA polymerases (métabolisme)</term>
<term>Données de séquences moléculaires</term>
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<term>Génétique inverse</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Mutation (génétique)</term>
<term>Protéines mutantes (métabolisme)</term>
<term>Protéines virales non structurales (métabolisme)</term>
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<term>Syndrome respiratoire aigu sévère (virologie)</term>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East respiratory syndrome highlight the potential lethality of zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess the largest known RNA virus genomes and encode a complex replication machinery consisting of 16 viral nonstructural proteins (nsps). Our study reveals that the SARS-coronavirus RNA polymerase (nsp12) needs to associate with nsp7 and nsp8 to activate its capability to replicate long RNA. Moreover, this complex associates with nsp14, the proofreading subunit required to safeguard coronavirus replication fidelity. Our study thus defines the core of an RNA-synthesizing machinery that is unique in the RNA virus world and includes several key targets for antiviral drug development.</p>
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