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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lysosomal Proteases Are a Determinant of Coronavirus Tropism</title><author><name sortKey="Zheng, Yuan" sort="Zheng, Yuan" uniqKey="Zheng Y" first="Yuan" last="Zheng">Yuan Zheng</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Chang" sort="Liu, Chang" uniqKey="Liu C" first="Chang" last="Liu">Chang Liu</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wan, Yushun" sort="Wan, Yushun" uniqKey="Wan Y" first="Yushun" last="Wan">Yushun Wan</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Geng, Qibin" sort="Geng, Qibin" uniqKey="Geng Q" first="Qibin" last="Geng">Qibin Geng</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wang, Michelle" sort="Wang, Michelle" uniqKey="Wang M" first="Michelle" last="Wang">Michelle Wang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30258004</idno><idno type="pmc">6258935</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258935</idno><idno type="RBID">PMC:6258935</idno><idno type="doi">10.1128/JVI.01504-18</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000C95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lysosomal Proteases Are a Determinant of Coronavirus Tropism</title><author><name sortKey="Zheng, Yuan" sort="Zheng, Yuan" uniqKey="Zheng Y" first="Yuan" last="Zheng">Yuan Zheng</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Shang, Jian" sort="Shang, Jian" uniqKey="Shang J" first="Jian" last="Shang">Jian Shang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Liu, Chang" sort="Liu, Chang" uniqKey="Liu C" first="Chang" last="Liu">Chang Liu</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wan, Yushun" sort="Wan, Yushun" uniqKey="Wan Y" first="Yushun" last="Wan">Yushun Wan</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Geng, Qibin" sort="Geng, Qibin" uniqKey="Geng Q" first="Qibin" last="Geng">Qibin Geng</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wang, Michelle" sort="Wang, Michelle" uniqKey="Wang M" first="Michelle" last="Wang">Michelle Wang</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph" sort="Baric, Ralph" uniqKey="Baric R" first="Ralph" last="Baric">Ralph Baric</name><affiliation><nlm:aff id="aff2"><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA</addr-line></nlm:aff></affiliation></author><author><name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name><affiliation><nlm:aff id="aff1"><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></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 are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.</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">30258004</article-id><article-id pub-id-type="pmc">6258935</article-id><article-id pub-id-type="publisher-id">JVI01504-18</article-id><article-id pub-id-type="doi">10.1128/JVI.01504-18</article-id><article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject></subj-group></article-categories><title-group><article-title>Lysosomal Proteases Are a Determinant of Coronavirus Tropism</article-title><alt-title alt-title-type="running-head">Coronavirus Tropism and Lysosomal Proteases</alt-title><alt-title alt-title-type="short-authors">Zheng et al.</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Zheng</surname><given-names>Yuan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Shang</surname><given-names>Jian</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Yang</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Liu</surname><given-names>Chang</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wan</surname><given-names>Yushun</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Geng</surname><given-names>Qibin</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Wang</surname><given-names>Michelle</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author" equal-contrib="no"><name><surname>Baric</surname><given-names>Ralph</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author" corresp="yes" equal-contrib="no"><name><surname>Li</surname><given-names>Fang</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><aff id="aff1"><label>a</label><addr-line>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA</addr-line></aff><aff id="aff2"><label>b</label><addr-line>Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA</addr-line></aff></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Gallagher</surname><given-names>Tom</given-names></name><role>Editor</role><aff>Loyola University Medical Center</aff></contrib></contrib-group><author-notes><corresp id="cor1">Address correspondence to Fang Li, <email>lifang@umn.edu</email>.</corresp><fn fn-type="equal"><p>Y.Z., J.S., and Y.Y. contributed equally to this work.</p></fn><fn fn-type="other"><p><bold>Citation</bold> Zheng Y, Shang J, Yang Y, Liu C, Wan Y, Geng Q, Wang M, Baric R, Li F. 2018. Lysosomal proteases are a determinant of coronavirus tropism. J Virol 92:e01504-18. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.01504-18">https://doi.org/10.1128/JVI.01504-18</ext-link>.</p></fn></author-notes><pub-date pub-type="epreprint"><day>26</day><month>9</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>27</day><month>11</month><year>2018</year></pub-date><pub-date pub-type="collection"><day>15</day><month>12</month><year>2018</year></pub-date><volume>92</volume><issue>24</issue><elocation-id>e01504-18</elocation-id><history><date date-type="received"><day>30</day><month>8</month><year>2018</year></date><date date-type="accepted"><day>19</day><month>9</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="zjv024184050001.pdf"></self-uri><abstract abstract-type="precis"><p>Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.</p></abstract><abstract><title>ABSTRACT</title><p>Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.</p><p><bold>IMPORTANCE</bold> Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.</p></abstract><kwd-group><title>KEYWORDS</title><kwd>coronavirus spike protein</kwd><kwd>lysosomal proteases</kwd><kwd>species tropism</kwd><kwd>tissue tropism</kwd></kwd-group><funding-group><award-group id="award1"><funding-source><institution-wrap><institution>HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)</institution><institution-id>https://doi.org/10.13039/100000060</institution-id></institution-wrap></funding-source><award-id>R01AI089728</award-id><principal-award-recipient><name><surname>Li</surname><given-names>Fang</given-names></name></principal-award-recipient></award-group><award-group id="award2"><funding-source><institution-wrap><institution>HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)</institution><institution-id>https://doi.org/10.13039/100000060</institution-id></institution-wrap></funding-source><award-id>R01AI110700</award-id><principal-award-recipient><name><surname>Li</surname><given-names>Fang</given-names></name></principal-award-recipient><principal-award-recipient><name><surname>Baric</surname><given-names>Ralph S.</given-names></name></principal-award-recipient></award-group></funding-group><counts><fig-count count="6"></fig-count><table-count count="0"></table-count><equation-count count="0"></equation-count><ref-count count="53"></ref-count><page-count count="14"></page-count><word-count count="9204"></word-count></counts><custom-meta-group><custom-meta><meta-name>cover-date</meta-name><meta-value>December 2018</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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