Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis
Identifieur interne : 003B67 ( Ncbi/Merge ); précédent : 003B66; suivant : 003B68Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis
Auteurs : Aaron Brice [Australie] ; Donna R. Whelan [Australie] ; Naoto Ito [Japon] ; Kenta Shimizu [Japon] ; Linda Wiltzer-Bach [Australie] ; Camden Y. Lo [Australie] ; Danielle Blondel [France] ; David A. Jans [Australie] ; Toby D. M. Bell [Australie] ; Gregory W. Moseley [Australie]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and
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DOI: 10.1038/srep33493
PubMed: 27649849
PubMed Central: 5030706
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Whelan</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ito, Naoto" sort="Ito, Naoto" uniqKey="Ito N" first="Naoto" last="Ito">Naoto Ito</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences</institution>, Gifu University, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shimizu, Kenta" sort="Shimizu, Kenta" uniqKey="Shimizu K" first="Kenta" last="Shimizu">Kenta Shimizu</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wiltzer Bach, Linda" sort="Wiltzer Bach, Linda" uniqKey="Wiltzer Bach L" first="Linda" last="Wiltzer-Bach">Linda Wiltzer-Bach</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lo, Camden Y" sort="Lo, Camden Y" uniqKey="Lo C" first="Camden Y." last="Lo">Camden Y. Lo</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Monash Micro Imaging</institution>, 27-31 Wright Street, Clayton, Victoria, 3168,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blondel, Danielle" sort="Blondel, Danielle" uniqKey="Blondel D" first="Danielle" last="Blondel">Danielle Blondel</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Unité de Virologie Moleculaire et Structurale</institution>, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jans, David A" sort="Jans, David A" uniqKey="Jans D" first="David A." last="Jans">David A. Jans</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bell, Toby D M" sort="Bell, Toby D M" uniqKey="Bell T" first="Toby D. M." last="Bell">Toby D. M. Bell</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moseley, Gregory W" sort="Moseley, Gregory W" uniqKey="Moseley G" first="Gregory W." last="Moseley">Gregory W. Moseley</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne</institution>, Melbourne, Victoria, 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and <italic>d</italic>STORM super-resolution microscopy to quantify protein interactions with the MT network and with individual MT filaments, we found that the interaction by Ni-CE-P3 is significantly impaired compared with Ni-P3. This correlated with an impaired capacity to effect association of the transcription factor STAT1 with MTs and to antagonize interferon (IFN)/STAT1-dependent antiviral signaling. Importantly, we identified a single mutation in Ni-CE-P3 that is sufficient to inhibit MT-association and IFN-antagonist function of Ni-P3, and showed that this mutation alone attenuates the pathogenicity of RABV. These data provide evidence that the viral protein-MT interface has important roles in pathogenesis, suggesting that this interface could provide targets for vaccine/antiviral drug development.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Allan, V J" uniqKey="Allan V">V. J. Allan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Forges, H" uniqKey="De Forges H">H. de Forges</name></author><author><name sortKey="Bouissou, A" uniqKey="Bouissou A">A. Bouissou</name></author><author><name sortKey="Perez, F" uniqKey="Perez F">F. Perez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirokawa, N" uniqKey="Hirokawa N">N. 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Ito</name></author></analytic></biblStruct></listBibl></div1></back></TEI><double pmid="27649849"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis</title><author><name sortKey="Brice, Aaron" sort="Brice, Aaron" uniqKey="Brice A" first="Aaron" last="Brice">Aaron Brice</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne</institution>, Melbourne, Victoria, 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Whelan, Donna R" sort="Whelan, Donna R" uniqKey="Whelan D" first="Donna R." last="Whelan">Donna R. Whelan</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ito, Naoto" sort="Ito, Naoto" uniqKey="Ito N" first="Naoto" last="Ito">Naoto Ito</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences</institution>, Gifu University, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shimizu, Kenta" sort="Shimizu, Kenta" uniqKey="Shimizu K" first="Kenta" last="Shimizu">Kenta Shimizu</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wiltzer Bach, Linda" sort="Wiltzer Bach, Linda" uniqKey="Wiltzer Bach L" first="Linda" last="Wiltzer-Bach">Linda Wiltzer-Bach</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lo, Camden Y" sort="Lo, Camden Y" uniqKey="Lo C" first="Camden Y." last="Lo">Camden Y. Lo</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Monash Micro Imaging</institution>, 27-31 Wright Street, Clayton, Victoria, 3168,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blondel, Danielle" sort="Blondel, Danielle" uniqKey="Blondel D" first="Danielle" last="Blondel">Danielle Blondel</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Unité de Virologie Moleculaire et Structurale</institution>, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jans, David A" sort="Jans, David A" uniqKey="Jans D" first="David A." last="Jans">David A. Jans</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bell, Toby D M" sort="Bell, Toby D M" uniqKey="Bell T" first="Toby D. M." last="Bell">Toby D. M. Bell</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moseley, Gregory W" sort="Moseley, Gregory W" uniqKey="Moseley G" first="Gregory W." last="Moseley">Gregory W. Moseley</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne</institution>, Melbourne, Victoria, 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27649849</idno><idno type="pmc">5030706</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030706</idno><idno type="RBID">PMC:5030706</idno><idno type="doi">10.1038/srep33493</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000844</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000844</idno><idno type="wicri:Area/Pmc/Curation">000843</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000843</idno><idno type="wicri:Area/Pmc/Checkpoint">000665</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000665</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis</title><author><name sortKey="Brice, Aaron" sort="Brice, Aaron" uniqKey="Brice A" first="Aaron" last="Brice">Aaron Brice</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne</institution>, Melbourne, Victoria, 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Whelan, Donna R" sort="Whelan, Donna R" uniqKey="Whelan D" first="Donna R." last="Whelan">Donna R. Whelan</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ito, Naoto" sort="Ito, Naoto" uniqKey="Ito N" first="Naoto" last="Ito">Naoto Ito</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences</institution>, Gifu University, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shimizu, Kenta" sort="Shimizu, Kenta" uniqKey="Shimizu K" first="Kenta" last="Shimizu">Kenta Shimizu</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>The United Graduate School of Veterinary Sciences, Gifu University</institution>, 1-1 Yanagido, Gifu 501-1193,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wiltzer Bach, Linda" sort="Wiltzer Bach, Linda" uniqKey="Wiltzer Bach L" first="Linda" last="Wiltzer-Bach">Linda Wiltzer-Bach</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lo, Camden Y" sort="Lo, Camden Y" uniqKey="Lo C" first="Camden Y." last="Lo">Camden Y. Lo</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Monash Micro Imaging</institution>, 27-31 Wright Street, Clayton, Victoria, 3168,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Blondel, Danielle" sort="Blondel, Danielle" uniqKey="Blondel D" first="Danielle" last="Blondel">Danielle Blondel</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Unité de Virologie Moleculaire et Structurale</institution>, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jans, David A" sort="Jans, David A" uniqKey="Jans D" first="David A." last="Jans">David A. Jans</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bell, Toby D M" sort="Bell, Toby D M" uniqKey="Bell T" first="Toby D. M." last="Bell">Toby D. M. Bell</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>School of Chemistry, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moseley, Gregory W" sort="Moseley, Gregory W" uniqKey="Moseley G" first="Gregory W." last="Moseley">Gregory W. Moseley</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne</institution>, Melbourne, Victoria, 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and <italic>d</italic>STORM super-resolution microscopy to quantify protein interactions with the MT network and with individual MT filaments, we found that the interaction by Ni-CE-P3 is significantly impaired compared with Ni-P3. This correlated with an impaired capacity to effect association of the transcription factor STAT1 with MTs and to antagonize interferon (IFN)/STAT1-dependent antiviral signaling. Importantly, we identified a single mutation in Ni-CE-P3 that is sufficient to inhibit MT-association and IFN-antagonist function of Ni-P3, and showed that this mutation alone attenuates the pathogenicity of RABV. These data provide evidence that the viral protein-MT interface has important roles in pathogenesis, suggesting that this interface could provide targets for vaccine/antiviral drug development.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Allan, V J" uniqKey="Allan V">V. J. Allan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Forges, H" uniqKey="De Forges H">H. de Forges</name></author><author><name sortKey="Bouissou, A" uniqKey="Bouissou A">A. Bouissou</name></author><author><name sortKey="Perez, F" uniqKey="Perez F">F. Perez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hirokawa, N" uniqKey="Hirokawa N">N. 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Whelan</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Ito, Naoto" sort="Ito, Naoto" uniqKey="Ito N" first="Naoto" last="Ito">Naoto Ito</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193</wicri:regionArea><orgName type="university">Université de Gifu</orgName><placeName><settlement type="city">Gifu (ville)</settlement><region type="province">Région du Chūbu</region><region type="prefecture">Préfecture de Gifu</region></placeName></affiliation></author><author><name sortKey="Shimizu, Kenta" sort="Shimizu, Kenta" uniqKey="Shimizu K" first="Kenta" last="Shimizu">Kenta Shimizu</name><affiliation wicri:level="4"><nlm:affiliation>The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193</wicri:regionArea><orgName type="university">Université de Gifu</orgName><placeName><settlement type="city">Gifu (ville)</settlement><region type="province">Région du Chūbu</region><region type="prefecture">Préfecture de Gifu</region></placeName></affiliation></author><author><name sortKey="Wiltzer Bach, Linda" sort="Wiltzer Bach, Linda" uniqKey="Wiltzer Bach L" first="Linda" last="Wiltzer-Bach">Linda Wiltzer-Bach</name><affiliation wicri:level="1"><nlm:affiliation>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Lo, Camden Y" sort="Lo, Camden Y" uniqKey="Lo C" first="Camden Y" last="Lo">Camden Y. Lo</name><affiliation wicri:level="1"><nlm:affiliation>Monash Micro Imaging, 27-31 Wright Street, Clayton, Victoria, 3168, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Micro Imaging, 27-31 Wright Street, Clayton, Victoria, 3168</wicri:regionArea><wicri:noRegion>3168</wicri:noRegion></affiliation></author><author><name sortKey="Blondel, Danielle" sort="Blondel, Danielle" uniqKey="Blondel D" first="Danielle" last="Blondel">Danielle Blondel</name><affiliation wicri:level="1"><nlm:affiliation>Unité de Virologie Moleculaire et Structurale, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Virologie Moleculaire et Structurale, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex</wicri:regionArea><wicri:noRegion>91198 Gif sur Yvette Cedex</wicri:noRegion><wicri:noRegion>91198 Gif sur Yvette Cedex</wicri:noRegion></affiliation></author><author><name sortKey="Jans, David A" sort="Jans, David A" uniqKey="Jans D" first="David A" last="Jans">David A. Jans</name><affiliation wicri:level="1"><nlm:affiliation>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Bell, Toby D M" sort="Bell, Toby D M" uniqKey="Bell T" first="Toby D M" last="Bell">Toby D M. Bell</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Moseley, Gregory W" sort="Moseley, Gregory W" uniqKey="Moseley G" first="Gregory W" last="Moseley">Gregory W. Moseley</name><affiliation wicri:level="4"><nlm:affiliation>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27649849</idno><idno type="pmid">27649849</idno><idno type="doi">10.1038/srep33493</idno><idno type="wicri:Area/PubMed/Corpus">001867</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001867</idno><idno type="wicri:Area/PubMed/Curation">001844</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001844</idno><idno type="wicri:Area/PubMed/Checkpoint">001844</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001844</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Quantitative Analysis of the Microtubule Interaction of Rabies Virus P3 Protein: Roles in Immune Evasion and Pathogenesis.</title><author><name sortKey="Brice, Aaron" sort="Brice, Aaron" uniqKey="Brice A" first="Aaron" last="Brice">Aaron Brice</name><affiliation wicri:level="4"><nlm:affiliation>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Whelan, Donna R" sort="Whelan, Donna R" uniqKey="Whelan D" first="Donna R" last="Whelan">Donna R. Whelan</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Ito, Naoto" sort="Ito, Naoto" uniqKey="Ito N" first="Naoto" last="Ito">Naoto Ito</name><affiliation wicri:level="4"><nlm:affiliation>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193</wicri:regionArea><orgName type="university">Université de Gifu</orgName><placeName><settlement type="city">Gifu (ville)</settlement><region type="province">Région du Chūbu</region><region type="prefecture">Préfecture de Gifu</region></placeName></affiliation></author><author><name sortKey="Shimizu, Kenta" sort="Shimizu, Kenta" uniqKey="Shimizu K" first="Kenta" last="Shimizu">Kenta Shimizu</name><affiliation wicri:level="4"><nlm:affiliation>The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193</wicri:regionArea><orgName type="university">Université de Gifu</orgName><placeName><settlement type="city">Gifu (ville)</settlement><region type="province">Région du Chūbu</region><region type="prefecture">Préfecture de Gifu</region></placeName></affiliation></author><author><name sortKey="Wiltzer Bach, Linda" sort="Wiltzer Bach, Linda" uniqKey="Wiltzer Bach L" first="Linda" last="Wiltzer-Bach">Linda Wiltzer-Bach</name><affiliation wicri:level="1"><nlm:affiliation>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Lo, Camden Y" sort="Lo, Camden Y" uniqKey="Lo C" first="Camden Y" last="Lo">Camden Y. Lo</name><affiliation wicri:level="1"><nlm:affiliation>Monash Micro Imaging, 27-31 Wright Street, Clayton, Victoria, 3168, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Monash Micro Imaging, 27-31 Wright Street, Clayton, Victoria, 3168</wicri:regionArea><wicri:noRegion>3168</wicri:noRegion></affiliation></author><author><name sortKey="Blondel, Danielle" sort="Blondel, Danielle" uniqKey="Blondel D" first="Danielle" last="Blondel">Danielle Blondel</name><affiliation wicri:level="1"><nlm:affiliation>Unité de Virologie Moleculaire et Structurale, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité de Virologie Moleculaire et Structurale, CNRS, UPR 3296, 91198 Gif sur Yvette Cedex</wicri:regionArea><wicri:noRegion>91198 Gif sur Yvette Cedex</wicri:noRegion><wicri:noRegion>91198 Gif sur Yvette Cedex</wicri:noRegion></affiliation></author><author><name sortKey="Jans, David A" sort="Jans, David A" uniqKey="Jans D" first="David A" last="Jans">David A. Jans</name><affiliation wicri:level="1"><nlm:affiliation>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Bell, Toby D M" sort="Bell, Toby D M" uniqKey="Bell T" first="Toby D M" last="Bell">Toby D M. Bell</name><affiliation wicri:level="1"><nlm:affiliation>School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>School of Chemistry, Monash University, Clayton, Victoria 3800</wicri:regionArea><wicri:noRegion>Victoria 3800</wicri:noRegion></affiliation></author><author><name sortKey="Moseley, Gregory W" sort="Moseley, Gregory W" uniqKey="Moseley G" first="Gregory W" last="Moseley">Gregory W. Moseley</name><affiliation wicri:level="4"><nlm:affiliation>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Viral Pathogenesis Laboratory, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although microtubules (MTs) are known to have important roles in intracellular transport of many viruses, a number of reports suggest that specific viral MT-associated proteins (MAPs) target MTs to subvert distinct MT-dependent cellular processes. The precise functional importance of these interactions and their roles in pathogenesis, however, remain largely unresolved. To assess the association with disease of the rabies virus (RABV) MAP, P3, we quantitatively compared the phenotypes of P3 from a pathogenic RABV strain, Nishigahara (Ni) and a non-pathogenic Ni-derivative strain, Ni-CE. Using confocal/live-cell imaging and dSTORM super-resolution microscopy to quantify protein interactions with the MT network and with individual MT filaments, we found that the interaction by Ni-CE-P3 is significantly impaired compared with Ni-P3. This correlated with an impaired capacity to effect association of the transcription factor STAT1 with MTs and to antagonize interferon (IFN)/STAT1-dependent antiviral signaling. Importantly, we identified a single mutation in Ni-CE-P3 that is sufficient to inhibit MT-association and IFN-antagonist function of Ni-P3, and showed that this mutation alone attenuates the pathogenicity of RABV. These data provide evidence that the viral protein-MT interface has important roles in pathogenesis, suggesting that this interface could provide targets for vaccine/antiviral drug development.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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