Transcriptional and Translational Landscape of Equine Torovirus
Identifieur interne : 001235 ( Pmc/Curation ); précédent : 001234; suivant : 001236Transcriptional and Translational Landscape of Equine Torovirus
Auteurs : Hazel Stewart [Royaume-Uni] ; Katherine Brown [Royaume-Uni] ; Adam M. Dinan [Royaume-Uni] ; Nerea Irigoyen [Royaume-Uni] ; Eric J. Snijder [Pays-Bas] ; Andrew E. Firth [Royaume-Uni]Source :
- Journal of Virology [ 0022-538X ] ; 2018.
Abstract
Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.
Url:
DOI: 10.1128/JVI.00589-18
PubMed: 29950409
PubMed Central: 6096809
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Dinan</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Virology, Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Irigoyen, Nerea" sort="Irigoyen, Nerea" uniqKey="Irigoyen N" first="Nerea" last="Irigoyen">Nerea Irigoyen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Virology, Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J." last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:aff id="aff2">Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Firth, Andrew E" sort="Firth, Andrew E" uniqKey="Firth A" first="Andrew E." last="Firth">Andrew E. Firth</name><affiliation wicri:level="1"><nlm:aff id="aff1">Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Virology, Department of Pathology, University of Cambridge, Cambridge</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Virol</journal-id><journal-id journal-id-type="iso-abbrev">J. Virol</journal-id><journal-id journal-id-type="hwp">jvi</journal-id><journal-id journal-id-type="pmc">jvi</journal-id><journal-id journal-id-type="publisher-id">JVI</journal-id><journal-title-group><journal-title>Journal of Virology</journal-title></journal-title-group><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology</publisher-name><publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29950409</article-id><article-id pub-id-type="pmc">6096809</article-id><article-id pub-id-type="publisher-id">00589-18</article-id><article-id pub-id-type="doi">10.1128/JVI.00589-18</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genome Replication and Regulation of Viral Gene Expression</subject></subj-group></article-categories><title-group><article-title>Transcriptional and Translational Landscape of Equine Torovirus</article-title><alt-title alt-title-type="running-head">Transcription and Translation of Equine Torovirus</alt-title><alt-title alt-title-type="short-authors">Stewart et al.</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Stewart</surname><given-names>Hazel</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Brown</surname><given-names>Katherine</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Dinan</surname><given-names>Adam M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Irigoyen</surname><given-names>Nerea</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Snijder</surname><given-names>Eric J.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0002-7986-9520</contrib-id><name><surname>Firth</surname><given-names>Andrew E.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><aff id="aff1"><label>a</label>Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom</aff><aff id="aff2"><label>b</label>Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Pfeiffer</surname><given-names>Julie K.</given-names></name><role>Editor</role><aff>University of Texas Southwestern Medical Center</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Andrew E. Firth, <email>aef24@cam.ac.uk</email>.</corresp><fn id="fn1" fn-type="present-address"><label>*</label><p>Present address: Adam M. Dinan, Fios Genomics, Edinburgh, United Kingdom.</p></fn><fn fn-type="equal"><p>H.S. and K.B. contributed equally to this work.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Stewart H, Brown K, Dinan AM, Irigoyen N, Snijder EJ, Firth AE. 2018. Transcriptional and translational landscape of equine torovirus. J Virol 92:e00589-18. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.00589-18">https://doi.org/10.1128/JVI.00589-18</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>27</day><month>6</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>16</day><month>8</month><year>2018</year></pub-date><pub-date pub-type="collection"><day>1</day><month>9</month><year>2018</year></pub-date><pub-date pub-type="pmc-release"><day>16</day><month>8</month><year>2018</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>92</volume><issue>17</issue><elocation-id>e00589-18</elocation-id><history><date date-type="received"><day>6</day><month>4</month><year>2018</year></date><date date-type="accepted"><day>13</day><month>6</month><year>2018</year></date></history><permissions><copyright-statement>Copyright © 2018 Stewart et al.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>Stewart et al.</copyright-holder><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="zjv017183828001.pdf"></self-uri><abstract abstract-type="precis"><p>Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.</p></abstract><abstract><title>ABSTRACT</title><p>The genus <named-content content-type="genus-species">Torovirus</named-content> (subfamily <named-content content-type="genus-species">Torovirinae</named-content>, family <named-content content-type="genus-species">Coronaviridae</named-content>, order <named-content content-type="genus-species">Nidovirales</named-content>) encompasses a range of species that infect domestic ungulates, including cattle, sheep, goats, pigs, and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV), we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyze the relative expression levels of the known torovirus proteins and transcripts, chimeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle), and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilizes a unique combination of discontinuous and nondiscontinuous RNA synthesis to produce its subgenomic RNAs (sgRNAs); indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated open reading frames (ORFs), located within the so-called 5′ untranslated region. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences, and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens.</p><p><bold>IMPORTANCE</bold> Toroviruses infect cattle, goats, pigs, and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine, and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens, including severe acute respiratory syndrome (SARS) coronavirus, and they share some common features; however, the mechanism that they use to produce sgRNA molecules differs. Here, we performed deep sequencing to determine how equine torovirus produces sgRNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>nidovirus</kwd><kwd>coronavirus</kwd><kwd>ribosomes</kwd><kwd>transcription</kwd><kwd>veterinary pathogens</kwd></kwd-group><funding-group><award-group id="award1"><funding-source id="gs1"><institution-wrap><institution>Wellcome Trust</institution></institution-wrap></funding-source><award-id rid="gs1">106207</award-id><principal-award-recipient><name><surname>Firth</surname><given-names>Andrew</given-names></name></principal-award-recipient></award-group><award-group id="award2"><funding-source id="gs2"><institution-wrap><institution>NWO-CW ECHO</institution></institution-wrap></funding-source><award-id rid="gs2">711.014.004</award-id><principal-award-recipient><name><surname>Snijder</surname><given-names>Eric J.</given-names></name></principal-award-recipient></award-group><award-group id="award3"><funding-source id="gs3"><institution-wrap><institution>EC | European Research Council (ERC)</institution><institution-id>https://doi.org/10.13039/501100000781</institution-id></institution-wrap></funding-source><award-id rid="gs3">646891</award-id><principal-award-recipient><name><surname>Firth</surname><given-names>Andrew</given-names></name></principal-award-recipient></award-group></funding-group><counts><count count="2" count-type="supplementary-material"></count><fig-count count="15"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="80"></ref-count><page-count count="24"></page-count><word-count count="12997"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>September 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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