Monitoring of S Protein Maturation in the Endoplasmic Reticulum by Calnexin Is Important for the Infectivity of Severe Acute Respiratory Syndrome Coronavirus
Identifieur interne : 000C74 ( Pmc/Corpus ); précédent : 000C73; suivant : 000C75Monitoring of S Protein Maturation in the Endoplasmic Reticulum by Calnexin Is Important for the Infectivity of Severe Acute Respiratory Syndrome Coronavirus
Auteurs : Masaya Fukushi ; Yoshiyuki Yoshinaka ; Yusuke Matsuoka ; Seisuke Hatakeyama ; Yukihito Ishizaka ; Teruo Kirikae ; Takehiko Sasazuki ; Tohru Miyoshi-AkiyamaSource :
- Journal of Virology [ 0022-538X ] ; 2012.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.
Url:
DOI: 10.1128/JVI.01250-12
PubMed: 22915798
PubMed Central: 3486308
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PMC:3486308Le document en format XML
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<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
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<affiliation><nlm:aff id="aff3">Deputy Director-General's Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan</nlm:aff>
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<author><name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name>
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<author><name sortKey="Hatakeyama, Seisuke" sort="Hatakeyama, Seisuke" uniqKey="Hatakeyama S" first="Seisuke" last="Hatakeyama">Seisuke Hatakeyama</name>
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<author><name sortKey="Miyoshi Akiyama, Tohru" sort="Miyoshi Akiyama, Tohru" uniqKey="Miyoshi Akiyama T" first="Tohru" last="Miyoshi-Akiyama">Tohru Miyoshi-Akiyama</name>
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<author><name sortKey="Fukushi, Masaya" sort="Fukushi, Masaya" uniqKey="Fukushi M" first="Masaya" last="Fukushi">Masaya Fukushi</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff3">Deputy Director-General's Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
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<affiliation><nlm:aff id="aff4">Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan</nlm:aff>
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<author><name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name>
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<author><name sortKey="Matsuoka, Yusuke" sort="Matsuoka, Yusuke" uniqKey="Matsuoka Y" first="Yusuke" last="Matsuoka">Yusuke Matsuoka</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
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<author><name sortKey="Hatakeyama, Seisuke" sort="Hatakeyama, Seisuke" uniqKey="Hatakeyama S" first="Seisuke" last="Hatakeyama">Seisuke Hatakeyama</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
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<author><name sortKey="Ishizaka, Yukihito" sort="Ishizaka, Yukihito" uniqKey="Ishizaka Y" first="Yukihito" last="Ishizaka">Yukihito Ishizaka</name>
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<author><name sortKey="Kirikae, Teruo" sort="Kirikae, Teruo" uniqKey="Kirikae T" first="Teruo" last="Kirikae">Teruo Kirikae</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sasazuki, Takehiko" sort="Sasazuki, Takehiko" uniqKey="Sasazuki T" first="Takehiko" last="Sasazuki">Takehiko Sasazuki</name>
<affiliation><nlm:aff id="aff7">National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
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<author><name sortKey="Miyoshi Akiyama, Tohru" sort="Miyoshi Akiyama, Tohru" uniqKey="Miyoshi Akiyama T" first="Tohru" last="Miyoshi-Akiyama">Tohru Miyoshi-Akiyama</name>
<affiliation><nlm:aff id="aff1">Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</nlm:aff>
</affiliation>
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<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
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<front><div type="abstract" xml:lang="en"><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.</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">22915798</article-id>
<article-id pub-id-type="pmc">3486308</article-id>
<article-id pub-id-type="publisher-id">01250-12</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01250-12</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Virus-Cell Interactions</subject>
</subj-group>
</article-categories>
<title-group><article-title>Monitoring of S Protein Maturation in the Endoplasmic Reticulum by Calnexin Is Important for the Infectivity of Severe Acute Respiratory Syndrome Coronavirus</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Fukushi</surname>
<given-names>Masaya</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<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>Yoshinaka</surname>
<given-names>Yoshiyuki</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Matsuoka</surname>
<given-names>Yusuke</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hatakeyama</surname>
<given-names>Seisuke</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ishizaka</surname>
<given-names>Yukihito</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kirikae</surname>
<given-names>Teruo</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sasazuki</surname>
<given-names>Takehiko</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Miyoshi-Akiyama</surname>
<given-names>Tohru</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<aff id="aff1"><label>a</label>
Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</aff>
<aff id="aff2"><label>b</label>
Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan</aff>
<aff id="aff3"><label>c</label>
Deputy Director-General's Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</aff>
<aff id="aff4"><label>d</label>
Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan</aff>
<aff id="aff5"><label>e</label>
Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan</aff>
<aff id="aff6"><label>f</label>
Department of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan</aff>
<aff id="aff7"><label>g</label>
National Center for Global Health and Medicine, Tokyo, Japan</aff>
</contrib-group>
<author-notes><corresp>Address correspondence to Masaya Fukushi, <email>mfukushi@hiroshima-u.ac.jp</email>
.</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>11</month>
<year>2012</year>
</pub-date>
<volume>86</volume>
<issue>21</issue>
<fpage>11745</fpage>
<lpage>11753</lpage>
<history><date date-type="received"><day>18</day>
<month>5</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>12</day>
<month>8</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjv02112011745.pdf"></self-uri>
<abstract><p>Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.</p>
</abstract>
</article-meta>
</front>
</pmc>
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