Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin.
Identifieur interne : 001285 ( Main/Exploration ); précédent : 001284; suivant : 001286Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin.
Auteurs : Kumari G. Lokugamage [États-Unis] ; Krishna Narayanan [États-Unis] ; Keisuke Nakagawa [États-Unis] ; Kaori Terasaki [États-Unis] ; Sydney I. Ramirez [États-Unis] ; Chien-Te K. Tseng [États-Unis] ; Shinji Makino [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2015.
Descripteurs français
- KwdFr :
- ARN messager (métabolisme), Amorces ADN, Cellules HEK293, Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Cytoplasme (métabolisme), Dipeptidyl peptidase 4 (métabolisme), Humains, Microscopie confocale, Noyau de la cellule (métabolisme), Plasmides (génétique), Protéines virales non structurales (métabolisme), RT-PCR, Réaction de polymérisation en chaine en temps réel, Régulation de l'expression des gènes (génétique), Technique de Northern, Technique de Western, Électroporation.
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Plasmides, Régulation de l'expression des gènes.
- métabolisme : ARN messager, Coronavirus du syndrome respiratoire du Moyen-Orient, Cytoplasme, Dipeptidyl peptidase 4, Noyau de la cellule, Protéines virales non structurales.
- Amorces ADN, Cellules HEK293, Humains, Microscopie confocale, RT-PCR, Réaction de polymérisation en chaine en temps réel, Technique de Northern, Technique de Western, Électroporation.
English descriptors
- KwdEn :
- Blotting, Northern, Blotting, Western, Cell Nucleus (metabolism), Cytoplasm (metabolism), DNA Primers, Dipeptidyl Peptidase 4 (metabolism), Electroporation, Gene Expression Regulation (genetics), HEK293 Cells, Humans, Microscopy, Confocal, Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (metabolism), Plasmids (genetics), RNA, Messenger (metabolism), Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , metabolism : Dipeptidyl Peptidase 4, RNA, Messenger, Viral Nonstructural Proteins.
- chemical : DNA Primers.
- genetics : Gene Expression Regulation, Middle East Respiratory Syndrome Coronavirus, Plasmids.
- metabolism : Cell Nucleus, Cytoplasm, Middle East Respiratory Syndrome Coronavirus.
- Blotting, Northern, Blotting, Western, Electroporation, HEK293 Cells, Humans, Microscopy, Confocal, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction.
Abstract
The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic human CoVs that share a property to inhibit host gene expression at the posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS-CoV that inhibits host gene expression at the translational level, we report that MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene expression by inhibiting host mRNA translation and inducing the degradation of host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of MERS-CoV nsp1, most probably triggered by its ability to induce an endonucleolytic RNA cleavage, was separable from its translation inhibitory function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly different strategy that selectively targeted translationally competent host mRNAs for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV nsp1 was distributed in both the nucleus and the cytoplasm and did not bind stably to the 40S subunit, suggesting a distinctly different mode of targeting translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1 selectively targeted mRNAs, which are transcribed in the nucleus and transported to the cytoplasm, for translation inhibition and mRNA degradation but spared exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that originate in the cytoplasm. Collectively, these data point toward a novel viral strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their escape from the inhibitory effects of MERS-CoV nsp1.
DOI: 10.1128/JVI.01352-15
PubMed: 26311885
Affiliations:
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Lokugamage</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Nakagawa, Keisuke" sort="Nakagawa, Keisuke" uniqKey="Nakagawa K" first="Keisuke" last="Nakagawa">Keisuke Nakagawa</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Terasaki, Kaori" sort="Terasaki, Kaori" uniqKey="Terasaki K" first="Kaori" last="Terasaki">Kaori Terasaki</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Ramirez, Sydney I" sort="Ramirez, Sydney I" uniqKey="Ramirez S" first="Sydney I" last="Ramirez">Sydney I. Ramirez</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA UTMB Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA UTMB Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA UTMB Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas, USA shmakino@utmb.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA UTMB Center for Tropical Diseases, The University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Blotting, Northern</term><term>Blotting, Western</term><term>Cell Nucleus (metabolism)</term><term>Cytoplasm (metabolism)</term><term>DNA Primers</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Electroporation</term><term>Gene Expression Regulation (genetics)</term><term>HEK293 Cells</term><term>Humans</term><term>Microscopy, Confocal</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>Plasmids (genetics)</term><term>RNA, Messenger (metabolism)</term><term>Real-Time Polymerase Chain Reaction</term><term>Reverse Transcriptase Polymerase Chain Reaction</term><term>Viral Nonstructural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (métabolisme)</term><term>Amorces ADN</term><term>Cellules HEK293</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term><term>Coronavirus du syndrome 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Transcriptase Polymerase Chain Reaction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Amorces ADN</term><term>Cellules HEK293</term><term>Humains</term><term>Microscopie confocale</term><term>RT-PCR</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Technique de Northern</term><term>Technique de Western</term><term>Électroporation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic human CoVs that share a property to inhibit host gene expression at the posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS-CoV that inhibits host gene expression at the translational level, we report that MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene expression by inhibiting host mRNA translation and inducing the degradation of host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of MERS-CoV nsp1, most probably triggered by its ability to induce an endonucleolytic RNA cleavage, was separable from its translation inhibitory function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly different strategy that selectively targeted translationally competent host mRNAs for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV nsp1 was distributed in both the nucleus and the cytoplasm and did not bind stably to the 40S subunit, suggesting a distinctly different mode of targeting translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1 selectively targeted mRNAs, which are transcribed in the nucleus and transported to the cytoplasm, for translation inhibition and mRNA degradation but spared exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that originate in the cytoplasm. Collectively, these data point toward a novel viral strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their escape from the inhibitory effects of MERS-CoV nsp1.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Lokugamage, Kumari G" sort="Lokugamage, Kumari G" uniqKey="Lokugamage K" first="Kumari G" last="Lokugamage">Kumari G. Lokugamage</name></region><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><name sortKey="Nakagawa, Keisuke" sort="Nakagawa, Keisuke" uniqKey="Nakagawa K" first="Keisuke" last="Nakagawa">Keisuke Nakagawa</name><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name><name sortKey="Ramirez, Sydney I" sort="Ramirez, Sydney I" uniqKey="Ramirez S" first="Sydney I" last="Ramirez">Sydney I. Ramirez</name><name sortKey="Terasaki, Kaori" sort="Terasaki, Kaori" uniqKey="Terasaki K" first="Kaori" last="Terasaki">Kaori Terasaki</name><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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