Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43
Identifieur interne : 000719 ( Pmc/Corpus ); précédent : 000718; suivant : 000720Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43
Auteurs : Mathieu Dubé ; Alain Le Coupanec ; Alan H. M. Wong ; James M. Rini ; Marc Desforges ; Pierre J. TalbotSource :
- Journal of Virology [ 0022-538X ] ; 2018.
Abstract
Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.
Url:
DOI: 10.1128/JVI.00404-18
PubMed: 29925652
PubMed Central: 6096804
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43</title><author><name sortKey="Dube, Mathieu" sort="Dube, Mathieu" uniqKey="Dube M" first="Mathieu" last="Dubé">Mathieu Dubé</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Le Coupanec, Alain" sort="Le Coupanec, Alain" uniqKey="Le Coupanec A" first="Alain" last="Le Coupanec">Alain Le Coupanec</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Wong, Alan H M" sort="Wong, Alan H M" uniqKey="Wong A" first="Alan H. M." last="Wong">Alan H. M. Wong</name><affiliation><nlm:aff id="aff2">Department of Biochemistry, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name><affiliation><nlm:aff id="aff2">Department of Biochemistry, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Desforges, Marc" sort="Desforges, Marc" uniqKey="Desforges M" first="Marc" last="Desforges">Marc Desforges</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Talbot, Pierre J" sort="Talbot, Pierre J" uniqKey="Talbot P" first="Pierre J." last="Talbot">Pierre J. Talbot</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29925652</idno><idno type="pmc">6096804</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096804</idno><idno type="RBID">PMC:6096804</idno><idno type="doi">10.1128/JVI.00404-18</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000719</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000719</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43</title><author><name sortKey="Dube, Mathieu" sort="Dube, Mathieu" uniqKey="Dube M" first="Mathieu" last="Dubé">Mathieu Dubé</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Le Coupanec, Alain" sort="Le Coupanec, Alain" uniqKey="Le Coupanec A" first="Alain" last="Le Coupanec">Alain Le Coupanec</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Wong, Alan H M" sort="Wong, Alan H M" uniqKey="Wong A" first="Alan H. M." last="Wong">Alan H. M. Wong</name><affiliation><nlm:aff id="aff2">Department of Biochemistry, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Rini, James M" sort="Rini, James M" uniqKey="Rini J" first="James M." last="Rini">James M. Rini</name><affiliation><nlm:aff id="aff2">Department of Biochemistry, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Desforges, Marc" sort="Desforges, Marc" uniqKey="Desforges M" first="Marc" last="Desforges">Marc Desforges</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</nlm:aff></affiliation></author><author><name sortKey="Talbot, Pierre J" sort="Talbot, Pierre J" uniqKey="Talbot P" first="Pierre J." last="Talbot">Pierre J. Talbot</name><affiliation><nlm:aff id="aff1">Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</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="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.</p></div></front></TEI><pmc article-type="research-article"><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">29925652</article-id><article-id pub-id-type="pmc">6096804</article-id><article-id pub-id-type="publisher-id">00404-18</article-id><article-id pub-id-type="doi">10.1128/JVI.00404-18</article-id><article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject></subj-group><subj-group subj-group-type="editorial-class"><subject>Spotlight</subject></subj-group></article-categories><title-group><article-title>Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43</article-title><alt-title alt-title-type="running-head">Neuron-to-Neuron Propagation of HCoV OC43</alt-title><alt-title alt-title-type="short-authors">Dubé et al.</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Dubé</surname><given-names>Mathieu</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Le Coupanec</surname><given-names>Alain</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wong</surname><given-names>Alan H. M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Rini</surname><given-names>James M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Desforges</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Talbot</surname><given-names>Pierre J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><aff id="aff1"><label>a</label>Laboratory of Neuroimmunovirology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada</aff><aff id="aff2"><label>b</label>Department of Biochemistry, University of Toronto, Toronto, ON, Canada</aff><aff id="aff3"><label>c</label>Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada</aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Diamond</surname><given-names>Michael S.</given-names></name><role>Editor</role><aff>Washington University School of Medicine</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Marc Desforges, <email>marc.desforges@iaf.inrs.ca</email>, or Pierre J. Talbot, <email>pierre.talbot@iaf.inrs.ca</email>.</corresp><fn fn-type="equal"><p>M. Dubé and A. Le Coupanec contributed equally to this article.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Dubé M, Le Coupanec A, Wong AHM, Rini JM, Desforges M, Talbot PJ. 2018. Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43. J Virol 92:e00404-18. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.00404-18">https://doi.org/10.1128/JVI.00404-18</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>20</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><volume>92</volume><issue>17</issue><elocation-id>e00404-18</elocation-id><history><date date-type="received"><day>7</day><month>3</month><year>2018</year></date><date date-type="accepted"><day>8</day><month>6</month><year>2018</year></date></history><permissions><copyright-statement>Copyright © 2018 American Society for Microbiology.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>American Society for Microbiology</copyright-holder><license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2"><license-p><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="zjv017183808001.pdf"></self-uri><abstract abstract-type="precis"><p>Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.</p></abstract><abstract><title>ABSTRACT</title><p>Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences.</p><p><bold>IMPORTANCE</bold> Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>central nervous system</kwd><kwd>coronavirus</kwd><kwd>encephalitis</kwd><kwd>neuroinvasion</kwd><kwd>neuropathogenesis</kwd><kwd>neuropropagation</kwd></kwd-group><funding-group><award-group id="award1"><funding-source id="gs1"><institution-wrap><institution>CIHR Institute of infection and immunity</institution></institution-wrap></funding-source><award-id rid="gs1">MT-9203</award-id><principal-award-recipient><name><surname>Talbot</surname><given-names>Pierre J.</given-names></name></principal-award-recipient></award-group></funding-group><counts><count count="6" count-type="supplementary-material"></count><fig-count count="8"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="78"></ref-count><page-count count="21"></page-count><word-count count="12737"></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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