Severe Acute Respiratory Syndrome Coronavirus nsp1 Facilitates Efficient Propagation in Cells through a Specific Translational Shutoff of Host mRNA
Identifieur interne : 001C70 ( Main/Merge ); précédent : 001C69; suivant : 001C71Severe Acute Respiratory Syndrome Coronavirus nsp1 Facilitates Efficient Propagation in Cells through a Specific Translational Shutoff of Host mRNA
Auteurs : Tomohisa Tanaka ; Wataru Kamitani ; Marta L. Dediego [Espagne] ; Luis Enjuanes [Espagne] ; Yoshiharu Matsuura [Japon]Source :
- Journal of Virology [ 0022-538X ] ; 2012.
Descripteurs français
- KwdFr :
- ARN messager (génétique), ARN messager (métabolisme), ARN non traduit (métabolisme), ARN viral (génétique), ARN viral (métabolisme), Cellules HEK293, Humains, Lignée cellulaire, Petite sous-unité du ribosome des eucaryotes (métabolisme), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), RNA replicase (génétique), RNA replicase (métabolisme), Régions 5' non traduites, Régulation de l'expression des gènes viraux, Réplication virale (génétique), Syndrome respiratoire aigu sévère (génétique), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (virologie), Séquences répétées inversées, Virus du SRAS (génétique), Virus du SRAS (métabolisme), Élongation de la traduction.
- MESH :
- génétique : ARN messager, ARN viral, Protéines virales non structurales, RNA replicase, Réplication virale, Syndrome respiratoire aigu sévère, Virus du SRAS.
- métabolisme : ARN messager, ARN non traduit, ARN viral, Petite sous-unité du ribosome des eucaryotes, Protéines virales non structurales, RNA replicase, Syndrome respiratoire aigu sévère, Virus du SRAS.
- virologie : Syndrome respiratoire aigu sévère.
- Cellules HEK293, Humains, Lignée cellulaire, Régions 5' non traduites, Régulation de l'expression des gènes viraux, Séquences répétées inversées, Élongation de la traduction.
English descriptors
- KwdEn :
- 5' Untranslated Regions, Cell Line, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inverted Repeat Sequences, Peptide Chain Elongation, Translational, RNA Replicase (genetics), RNA Replicase (metabolism), RNA, Messenger (genetics), RNA, Messenger (metabolism), RNA, Untranslated (metabolism), RNA, Viral (genetics), RNA, Viral (metabolism), Ribosome Subunits, Small, Eukaryotic (metabolism), SARS Virus (genetics), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (genetics), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (virology), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Virus Replication (genetics).
- MESH :
- chemical , genetics : RNA Replicase, RNA, Messenger, RNA, Viral, Viral Nonstructural Proteins.
- chemical , metabolism : RNA Replicase, RNA, Messenger, RNA, Untranslated, RNA, Viral, Viral Nonstructural Proteins.
- chemical : 5' Untranslated Regions.
- genetics : SARS Virus, Severe Acute Respiratory Syndrome, Virus Replication.
- metabolism : Ribosome Subunits, Small, Eukaryotic, SARS Virus, Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Cell Line, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Inverted Repeat Sequences, Peptide Chain Elongation, Translational.
Abstract
Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a set of common 5′ and 3′ untranslated regions (UTR) are synthesized from the incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1 protein causes a severe translational shutoff by binding to the 40S ribosomal subunits. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5′UTR of host mRNA. However, the mechanism by which SCoV viral proteins are efficiently produced in infected cells in which host protein synthesis is impaired by nsp1 is unknown. In this study, we investigated the role of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities were significantly suppressed in cells expressing nsp1 together with the mRNA carrying a luciferase gene, while nsp1 failed to suppress luciferase activities of the mRNA flanked by the 5′UTR of SCoV. An RNA-protein binding assay and RNA decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5′UTR of SCoV RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1. Furthermore, experiments using an SCoV replicon system showed that the specific interaction enhanced the SCoV replication. The specific interaction of nsp1 with SL1 is an important strategy to facilitate efficient viral gene expression in infected cells, in which nsp1 suppresses host gene expression. Our data indicate a novel mechanism of viral gene expression control by nsp1 and give new insight into understanding the pathogenesis of SARS.
Url:
DOI: 10.1128/JVI.01700-12
PubMed: 22855488
PubMed Central: 3457165
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PMC:3457165Le document en format XML
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(genetics)</term><term>Viral Nonstructural Proteins (metabolism)</term><term>Virus Replication (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (génétique)</term><term>ARN messager (métabolisme)</term><term>ARN non traduit (métabolisme)</term><term>ARN viral (génétique)</term><term>ARN viral (métabolisme)</term><term>Cellules HEK293</term><term>Humains</term><term>Lignée cellulaire</term><term>Petite sous-unité du ribosome des eucaryotes (métabolisme)</term><term>Protéines virales non structurales (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>RNA replicase (génétique)</term><term>RNA replicase (métabolisme)</term><term>Régions 5' non traduites</term><term>Régulation de l'expression des gènes viraux</term><term>Réplication virale (génétique)</term><term>Syndrome respiratoire aigu sévère (génétique)</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Séquences répétées inversées</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term><term>Élongation de la traduction</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>RNA Replicase</term><term>RNA, Messenger</term><term>RNA, Viral</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA Replicase</term><term>RNA, Messenger</term><term>RNA, Untranslated</term><term>RNA, Viral</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>5' Untranslated Regions</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ARN messager</term><term>ARN 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xml:lang="en"><term>Cell Line</term><term>Gene Expression Regulation, Viral</term><term>HEK293 Cells</term><term>Humans</term><term>Inverted Repeat Sequences</term><term>Peptide Chain Elongation, Translational</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HEK293</term><term>Humains</term><term>Lignée cellulaire</term><term>Régions 5' non traduites</term><term>Régulation de l'expression des gènes viraux</term><term>Séquences répétées inversées</term><term>Élongation de la traduction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a set of common 5′ and 3′ untranslated regions (UTR) are synthesized from the incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1 protein causes a severe translational shutoff by binding to the 40S ribosomal subunits. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5′UTR of host mRNA. However, the mechanism by which SCoV viral proteins are efficiently produced in infected cells in which host protein synthesis is impaired by nsp1 is unknown. In this study, we investigated the role of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities were significantly suppressed in cells expressing nsp1 together with the mRNA carrying a luciferase gene, while nsp1 failed to suppress luciferase activities of the mRNA flanked by the 5′UTR of SCoV. An RNA-protein binding assay and RNA decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5′UTR of SCoV RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1. Furthermore, experiments using an SCoV replicon system showed that the specific interaction enhanced the SCoV replication. The specific interaction of nsp1 with SL1 is an important strategy to facilitate efficient viral gene expression in infected cells, in which nsp1 suppresses host gene expression. Our data indicate a novel mechanism of viral gene expression control by nsp1 and give new insight into understanding the pathogenesis of SARS.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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