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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication</title><author><name sortKey="Zhao, Yongqian" sort="Zhao, Yongqian" uniqKey="Zhao Y" first="Yongqian" last="Zhao">Yongqian Zhao</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Soh, Tingjin Sherryl" sort="Soh, Tingjin Sherryl" uniqKey="Soh T" first="Tingjin Sherryl" last="Soh">Tingjin Sherryl Soh</name><affiliation><nlm:aff id="aff3">School of Biological Sciences, Nanyang Technological University, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Chan, Kitti Wing Ki" sort="Chan, Kitti Wing Ki" uniqKey="Chan K" first="Kitti Wing Ki" last="Chan">Kitti Wing Ki Chan</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fung, Sarah Suet Yin" sort="Fung, Sarah Suet Yin" uniqKey="Fung S" first="Sarah Suet Yin" last="Fung">Sarah Suet Yin Fung</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Swaminathan, Kunchithapadam" sort="Swaminathan, Kunchithapadam" uniqKey="Swaminathan K" first="Kunchithapadam" last="Swaminathan">Kunchithapadam Swaminathan</name><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Department of Biological Sciences, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lim, Siew Pheng" sort="Lim, Siew Pheng" uniqKey="Lim S" first="Siew Pheng" last="Lim">Siew Pheng Lim</name><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Shi, Pei Yong" sort="Shi, Pei Yong" uniqKey="Shi P" first="Pei-Yong" last="Shi">Pei-Yong Shi</name><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Huber, Thomas" sort="Huber, Thomas" uniqKey="Huber T" first="Thomas" last="Huber">Thomas Huber</name><affiliation><nlm:aff id="aff6">Research School of Chemistry, Australian National University, Canberra, Australia</nlm:aff></affiliation></author><author><name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name><affiliation><nlm:aff id="aff3">School of Biological Sciences, Nanyang Technological University, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">UPMC UMRS CR7-CNRS ERL 8255-INSERM U1135 Centre d'Immunologie et des Maladies Infectieuses, Centre Hospitalier Universitaire Pitié-Salpêtrière, Faculté de Médecine Pierre et Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Luo, Dahai" sort="Luo, Dahai" uniqKey="Luo D" first="Dahai" last="Luo">Dahai Luo</name><affiliation><nlm:aff id="aff8">Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore</nlm:aff></affiliation></author><author><name sortKey="Vasudevan, Subhash G" sort="Vasudevan, Subhash G" uniqKey="Vasudevan S" first="Subhash G." last="Vasudevan">Subhash G. Vasudevan</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26269182</idno><idno type="pmc">4580200</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580200</idno><idno type="RBID">PMC:4580200</idno><idno type="doi">10.1128/JVI.01239-15</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000155</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000155</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication</title><author><name sortKey="Zhao, Yongqian" sort="Zhao, Yongqian" uniqKey="Zhao Y" first="Yongqian" last="Zhao">Yongqian Zhao</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Soh, Tingjin Sherryl" sort="Soh, Tingjin Sherryl" uniqKey="Soh T" first="Tingjin Sherryl" last="Soh">Tingjin Sherryl Soh</name><affiliation><nlm:aff id="aff3">School of Biological Sciences, Nanyang Technological University, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Chan, Kitti Wing Ki" sort="Chan, Kitti Wing Ki" uniqKey="Chan K" first="Kitti Wing Ki" last="Chan">Kitti Wing Ki Chan</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fung, Sarah Suet Yin" sort="Fung, Sarah Suet Yin" uniqKey="Fung S" first="Sarah Suet Yin" last="Fung">Sarah Suet Yin Fung</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation></author><author><name sortKey="Swaminathan, Kunchithapadam" sort="Swaminathan, Kunchithapadam" uniqKey="Swaminathan K" first="Kunchithapadam" last="Swaminathan">Kunchithapadam Swaminathan</name><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff5">Department of Biological Sciences, National University of Singapore, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lim, Siew Pheng" sort="Lim, Siew Pheng" uniqKey="Lim S" first="Siew Pheng" last="Lim">Siew Pheng Lim</name><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Shi, Pei Yong" sort="Shi, Pei Yong" uniqKey="Shi P" first="Pei-Yong" last="Shi">Pei-Yong Shi</name><affiliation><nlm:aff id="aff4">Novartis Institute for Tropical Diseases, Singapore</nlm:aff></affiliation></author><author><name sortKey="Huber, Thomas" sort="Huber, Thomas" uniqKey="Huber T" first="Thomas" last="Huber">Thomas Huber</name><affiliation><nlm:aff id="aff6">Research School of Chemistry, Australian National University, Canberra, Australia</nlm:aff></affiliation></author><author><name sortKey="Lescar, Julien" sort="Lescar, Julien" uniqKey="Lescar J" first="Julien" last="Lescar">Julien Lescar</name><affiliation><nlm:aff id="aff3">School of Biological Sciences, Nanyang Technological University, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">UPMC UMRS CR7-CNRS ERL 8255-INSERM U1135 Centre d'Immunologie et des Maladies Infectieuses, Centre Hospitalier Universitaire Pitié-Salpêtrière, Faculté de Médecine Pierre et Marie Curie, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Luo, Dahai" sort="Luo, Dahai" uniqKey="Luo D" first="Dahai" last="Luo">Dahai Luo</name><affiliation><nlm:aff id="aff8">Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore</nlm:aff></affiliation></author><author><name sortKey="Vasudevan, Subhash G" sort="Vasudevan, Subhash G" uniqKey="Vasudevan S" first="Subhash G." last="Vasudevan">Subhash G. Vasudevan</name><affiliation><nlm:aff id="aff1">Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</nlm:aff></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="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.</p></div></front></TEI><pmc article-type="brief-report"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<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">26269182</article-id><article-id pub-id-type="pmc">4580200</article-id><article-id pub-id-type="publisher-id">01239-15</article-id><article-id pub-id-type="doi">10.1128/JVI.01239-15</article-id><article-categories><subj-group subj-group-type="heading"><subject>Structure and Assembly</subject></subj-group></article-categories><title-group><article-title>Flexibility of NS5 Methyltransferase-Polymerase Linker Region Is Essential for Dengue Virus Replication</article-title><alt-title alt-title-type="running-head">Conformational Regulation by NS5 Linker</alt-title><alt-title alt-title-type="short-authors">Zhao et al.</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Yongqian</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Soh</surname><given-names>Tingjin Sherryl</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Kitti Wing Ki</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fung</surname><given-names>Sarah Suet Yin</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Swaminathan</surname><given-names>Kunchithapadam</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Siew Pheng</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Pei-Yong</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huber</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lescar</surname><given-names>Julien</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="aff" rid="aff7"><sup>g</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Luo</surname><given-names>Dahai</given-names></name><xref ref-type="aff" rid="aff8"><sup>h</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Vasudevan</surname><given-names>Subhash G.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><aff id="aff1"><label>a</label>Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore</aff><aff id="aff2"><label>b</label>NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore</aff><aff id="aff3"><label>c</label>School of Biological Sciences, Nanyang Technological University, Singapore</aff><aff id="aff4"><label>d</label>Novartis Institute for Tropical Diseases, Singapore</aff><aff id="aff5"><label>e</label>Department of Biological Sciences, National University of Singapore, Singapore</aff><aff id="aff6"><label>f</label>Research School of Chemistry, Australian National University, Canberra, Australia</aff><aff id="aff7"><label>g</label>UPMC UMRS CR7-CNRS ERL 8255-INSERM U1135 Centre d'Immunologie et des Maladies Infectieuses, Centre Hospitalier Universitaire Pitié-Salpêtrière, Faculté de Médecine Pierre et Marie Curie, Paris, France</aff><aff id="aff8"><label>h</label>Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Diamond</surname><given-names>M. S.</given-names></name><role>Editor</role></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Dahai Luo, <email>luodahai@ntu.edu.sg</email>, or Subhash G. Vasudevan, <email>subhash.vasudevan@duke-nus.edu.sg</email>.</corresp><fn fn-type="other"><p><bold>Citation</bold> Zhao Y, Soh TS, Chan KWK, Fung SSY, Swaminathan K, Lim SP, Shi P-Y, Huber T, Lescar J, Luo D, Vasudevan SG. 2015. Flexibility of NS5 methyltransferase-polymerase linker region is essential for dengue virus replication. J Virol 89:10717–10721. doi:<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1128/JVI.01239-15">10.1128/JVI.01239-15</ext-link>.</p></fn></author-notes><pub-date pub-type="epub"><day>12</day><month>8</month><year>2015</year></pub-date><pub-date pub-type="collection"><day>15</day><month>10</month><year>2015</year></pub-date><volume>89</volume><issue>20</issue><fpage>10717</fpage><lpage>10721</lpage><history><date date-type="received"><day>13</day><month>5</month><year>2015</year></date><date date-type="accepted"><day>3</day><month>8</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder></permissions><self-uri content-type="pdf" xlink:href="zjv02015010717.pdf"></self-uri><abstract><p>We examined the function of the conserved Val/Ile residue within the dengue virus NS5 interdomain linker (residues 263 to 272) by site-directed mutagenesis. Gly substitution or Gly/Pro insertion after the conserved residue increased the linker flexibility and created slightly attenuated viruses. In contrast, Pro substitution abolished virus replication by imposing rigidity in the linker and restricting NS5's conformational plasticity. Our biochemical and reverse genetics experiments demonstrate that NS5 utilizes conformational regulation to achieve optimum viral replication.</p></abstract><counts><fig-count count="4"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="23"></ref-count><page-count count="5"></page-count><word-count count="3097"></word-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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