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 : 001490 ( PubMed/Curation ); précédent : 001489; suivant : 001491Middle 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
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Lokugamage</name><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Narayanan, Krishna" sort="Narayanan, Krishna" uniqKey="Narayanan K" first="Krishna" last="Narayanan">Krishna Narayanan</name><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Nakagawa, Keisuke" sort="Nakagawa, Keisuke" uniqKey="Nakagawa K" first="Keisuke" last="Nakagawa">Keisuke Nakagawa</name><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Terasaki, Kaori" sort="Terasaki, Kaori" uniqKey="Terasaki K" first="Kaori" last="Terasaki">Kaori Terasaki</name><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Ramirez, Sydney I" sort="Ramirez, Sydney I" uniqKey="Ramirez S" first="Sydney I" last="Ramirez">Sydney I. 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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></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 respiratoire du Moyen-Orient (métabolisme)</term><term>Cytoplasme (métabolisme)</term><term>Dipeptidyl peptidase 4 (métabolisme)</term><term>Humains</term><term>Microscopie confocale</term><term>Noyau de la cellule (métabolisme)</term><term>Plasmides (génétique)</term><term>Protéines virales non structurales (métabolisme)</term><term>RT-PCR</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Régulation de l'expression des gènes (génétique)</term><term>Technique de Northern</term><term>Technique de Western</term><term>Électroporation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>RNA, Messenger</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>DNA Primers</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Gene Expression Regulation</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Plasmids</term></keywords><keywords 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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><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26311885</PMID><DateCompleted><Year>2016</Year><Month>01</Month><Day>19</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>89</Volume><Issue>21</Issue><PubDate><Year>2015</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin.</ArticleTitle><Pagination><MedlinePgn>10970-81</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01352-15</ELocationID><Abstract><AbstractText Label="UNLABELLED">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.</AbstractText><AbstractText Label="IMPORTANCE" NlmCategory="OBJECTIVE">Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human CoV that emerged in Saudi Arabia in 2012. MERS-CoV has a zoonotic origin and poses a major threat to public health. However, little is known about the viral factors contributing to the high virulence of MERS-CoV. Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors. The nonstructural protein 1 (nsp1) of CoVs is one such protein that inhibits host gene expression and is a major virulence factor. This study presents evidence for a strategy used by MERS-CoV nsp1 to inhibit host gene expression that has not been described previously for any viral protein. The present study represents a meaningful step toward a better understanding of the factors and molecular mechanisms governing the virulence and pathogenesis of MERS-CoV.</AbstractText><CopyrightInformation>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lokugamage</LastName><ForeName>Kumari G</ForeName><Initials>KG</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Narayanan</LastName><ForeName>Krishna</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nakagawa</LastName><ForeName>Keisuke</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Terasaki</LastName><ForeName>Kaori</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ramirez</LastName><ForeName>Sydney I</ForeName><Initials>SI</Initials><AffiliationInfo><Affiliation>Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tseng</LastName><ForeName>Chien-Te K</ForeName><Initials>CT</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Makino</LastName><ForeName>Shinji</ForeName><Initials>S</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>AI101772</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI99107</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI117445</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AI117445</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI114657</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI099107</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AI101772</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI114657</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH 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