Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus.
Identifieur interne : 004791 ( Main/Exploration ); précédent : 004790; suivant : 004792Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus.
Auteurs : Eric Bergeron [Canada] ; Martin J. Vincent ; Louise Wickham ; Josée Hamelin ; Ajoy Basak ; Stuart T. Nichol ; Michel Chrétien ; Nabil G. SeidahSource :
- Biochemical and biophysical research communications [ 0006-291X ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Furine (génétique), Furine (métabolisme), Humains, Mutation, Proprotein convertase 5 (génétique), Proprotein convertase 5 (métabolisme), Proprotein convertases (métabolisme), Subtilisines (génétique), Subtilisines (métabolisme), Syndrome respiratoire aigu sévère (enzymologie), Syndrome respiratoire aigu sévère (métabolisme), Syndrome respiratoire aigu sévère (transmission), Virus du SRAS (enzymologie), Virus du SRAS (génétique), Virus du SRAS (métabolisme).
- MESH :
- enzymologie : Syndrome respiratoire aigu sévère, Virus du SRAS.
- génétique : Furine, Proprotein convertase 5, Subtilisines, Virus du SRAS.
- métabolisme : Furine, Proprotein convertase 5, Proprotein convertases, Subtilisines, Syndrome respiratoire aigu sévère, Virus du SRAS.
- transmission : Animaux, Cellules Vero, Humains, Mutation, Syndrome respiratoire aigu sévère.
English descriptors
- KwdEn :
- Animals, Chlorocebus aethiops, Furin (genetics), Furin (metabolism), Humans, Mutation, Proprotein Convertase 5 (genetics), Proprotein Convertase 5 (metabolism), Proprotein Convertases (metabolism), SARS Virus (enzymology), SARS Virus (genetics), SARS Virus (metabolism), Severe Acute Respiratory Syndrome (enzymology), Severe Acute Respiratory Syndrome (metabolism), Severe Acute Respiratory Syndrome (transmission), Subtilisins (genetics), Subtilisins (metabolism), Vero Cells.
- MESH :
- chemical , genetics : Furin, Proprotein Convertase 5, Subtilisins.
- chemical , metabolism : Furin, Proprotein Convertase 5, Proprotein Convertases, Subtilisins.
- enzymology : SARS Virus, Severe Acute Respiratory Syndrome.
- genetics : SARS Virus.
- metabolism : SARS Virus, Severe Acute Respiratory Syndrome.
- transmission : Severe Acute Respiratory Syndrome.
- Animals, Chlorocebus aethiops, Humans, Mutation, Vero Cells.
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a approximately 190 kDa endoplasmic reticulum form and a approximately 210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of approximately 110 and approximately 80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the approximately 80 kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg(761) of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.
DOI: 10.1016/j.bbrc.2004.11.063
PubMed: 15596135
Affiliations:
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Le document en format XML
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Vincent</name></author><author><name sortKey="Wickham, Louise" sort="Wickham, Louise" uniqKey="Wickham L" first="Louise" last="Wickham">Louise Wickham</name></author><author><name sortKey="Hamelin, Josee" sort="Hamelin, Josee" uniqKey="Hamelin J" first="Josée" last="Hamelin">Josée Hamelin</name></author><author><name sortKey="Basak, Ajoy" sort="Basak, Ajoy" uniqKey="Basak A" first="Ajoy" last="Basak">Ajoy Basak</name></author><author><name sortKey="Nichol, Stuart T" sort="Nichol, Stuart T" uniqKey="Nichol S" first="Stuart T" last="Nichol">Stuart T. Nichol</name></author><author><name sortKey="Chretien, Michel" sort="Chretien, Michel" uniqKey="Chretien M" first="Michel" last="Chrétien">Michel Chrétien</name></author><author><name sortKey="Seidah, Nabil G" sort="Seidah, Nabil G" uniqKey="Seidah N" first="Nabil G" last="Seidah">Nabil G. 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Vincent</name></author><author><name sortKey="Wickham, Louise" sort="Wickham, Louise" uniqKey="Wickham L" first="Louise" last="Wickham">Louise Wickham</name></author><author><name sortKey="Hamelin, Josee" sort="Hamelin, Josee" uniqKey="Hamelin J" first="Josée" last="Hamelin">Josée Hamelin</name></author><author><name sortKey="Basak, Ajoy" sort="Basak, Ajoy" uniqKey="Basak A" first="Ajoy" last="Basak">Ajoy Basak</name></author><author><name sortKey="Nichol, Stuart T" sort="Nichol, Stuart T" uniqKey="Nichol S" first="Stuart T" last="Nichol">Stuart T. Nichol</name></author><author><name sortKey="Chretien, Michel" sort="Chretien, Michel" uniqKey="Chretien M" first="Michel" last="Chrétien">Michel Chrétien</name></author><author><name sortKey="Seidah, Nabil G" sort="Seidah, Nabil G" uniqKey="Seidah N" first="Nabil G" last="Seidah">Nabil G. Seidah</name></author></analytic><series><title level="j">Biochemical and biophysical research communications</title><idno type="ISSN">0006-291X</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Furin (genetics)</term><term>Furin (metabolism)</term><term>Humans</term><term>Mutation</term><term>Proprotein Convertase 5 (genetics)</term><term>Proprotein Convertase 5 (metabolism)</term><term>Proprotein Convertases (metabolism)</term><term>SARS Virus (enzymology)</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>Severe Acute Respiratory Syndrome (enzymology)</term><term>Severe Acute Respiratory Syndrome (metabolism)</term><term>Severe Acute Respiratory Syndrome (transmission)</term><term>Subtilisins (genetics)</term><term>Subtilisins (metabolism)</term><term>Vero Cells</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Furine (génétique)</term><term>Furine (métabolisme)</term><term>Humains</term><term>Mutation</term><term>Proprotein convertase 5 (génétique)</term><term>Proprotein convertase 5 (métabolisme)</term><term>Proprotein convertases (métabolisme)</term><term>Subtilisines (génétique)</term><term>Subtilisines (métabolisme)</term><term>Syndrome respiratoire aigu sévère (enzymologie)</term><term>Syndrome respiratoire aigu sévère (métabolisme)</term><term>Syndrome respiratoire aigu sévère (transmission)</term><term>Virus du SRAS (enzymologie)</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Furin</term><term>Proprotein Convertase 5</term><term>Subtilisins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Furin</term><term>Proprotein Convertase 5</term><term>Proprotein Convertases</term><term>Subtilisins</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Furine</term><term>Proprotein convertase 5</term><term>Subtilisines</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Furine</term><term>Proprotein convertase 5</term><term>Proprotein convertases</term><term>Subtilisines</term><term>Syndrome respiratoire aigu sévère</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="transmission" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Chlorocebus aethiops</term><term>Humans</term><term>Mutation</term><term>Vero Cells</term></keywords><keywords scheme="MESH" qualifier="transmission" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Humains</term><term>Mutation</term><term>Syndrome respiratoire aigu sévère</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a approximately 190 kDa endoplasmic reticulum form and a approximately 210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of approximately 110 and approximately 80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the approximately 80 kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg(761) of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Basak, Ajoy" sort="Basak, Ajoy" uniqKey="Basak A" first="Ajoy" last="Basak">Ajoy Basak</name><name sortKey="Chretien, Michel" sort="Chretien, Michel" uniqKey="Chretien M" first="Michel" last="Chrétien">Michel Chrétien</name><name sortKey="Hamelin, Josee" sort="Hamelin, Josee" uniqKey="Hamelin J" first="Josée" last="Hamelin">Josée Hamelin</name><name sortKey="Nichol, Stuart T" sort="Nichol, Stuart T" uniqKey="Nichol S" first="Stuart T" last="Nichol">Stuart T. Nichol</name><name sortKey="Seidah, Nabil G" sort="Seidah, Nabil G" uniqKey="Seidah N" first="Nabil G" last="Seidah">Nabil G. Seidah</name><name sortKey="Vincent, Martin J" sort="Vincent, Martin J" uniqKey="Vincent M" first="Martin J" last="Vincent">Martin J. Vincent</name><name sortKey="Wickham, Louise" sort="Wickham, Louise" uniqKey="Wickham L" first="Louise" last="Wickham">Louise Wickham</name></noCountry><country name="Canada"><noRegion><name sortKey="Bergeron, Eric" sort="Bergeron, Eric" uniqKey="Bergeron E" first="Eric" last="Bergeron">Eric Bergeron</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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