Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells.
Identifieur interne : 002A48 ( Main/Exploration ); précédent : 002A47; suivant : 002A49Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells.
Auteurs : Yoshiyuki Yamada ; Ding Xiang LiuSource :
- Journal of virology [ 1098-5514 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Cellules Vero, Cellules géantes (virologie), Furine (métabolisme), Fusion cellulaire, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (métabolisme), Motifs d'acides aminés, Mutagenèse dirigée, Protéines de l'enveloppe virale (métabolisme), Pénétration virale, Substitution d'acide aminé, Virus de la bronchite infectieuse (physiologie).
- MESH :
- métabolisme : Furine, Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- physiologie : Virus de la bronchite infectieuse.
- virologie : Cellules géantes.
- Animaux, Cellules Vero, Fusion cellulaire, Glycoprotéine de spicule des coronavirus, Motifs d'acides aminés, Mutagenèse dirigée, Pénétration virale, Substitution d'acide aminé.
English descriptors
- KwdEn :
- Amino Acid Motifs, Amino Acid Substitution, Animals, Cell Fusion, Chlorocebus aethiops, Furin (metabolism), Giant Cells (virology), Infectious bronchitis virus (physiology), Membrane Glycoproteins (metabolism), Mutagenesis, Site-Directed, Spike Glycoprotein, Coronavirus, Vero Cells, Viral Envelope Proteins (metabolism), Virus Internalization.
- MESH :
- chemical , metabolism : Furin, Membrane Glycoproteins, Viral Envelope Proteins.
- physiology : Infectious bronchitis virus.
- virology : Giant Cells.
- Amino Acid Motifs, Amino Acid Substitution, Animals, Cell Fusion, Chlorocebus aethiops, Mutagenesis, Site-Directed, Spike Glycoprotein, Coronavirus, Vero Cells, Virus Internalization.
Abstract
The spike (S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR(537)/S in virus-infected cells. In this study, we observe that the S2 subunit of the IBV Beaudette strain is additionally cleaved at the second furin site (RRRR(690)/S) in cells expressing S constructs and in virus-infected cells. Detailed time course experiments showed that a peptide furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, blocked both viral entry and syncytium formation. Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry. Instead, a yet-to-be-identified serine protease(s) was involved, as revealed by protease inhibitor studies. Furthermore, sequence analysis of CoV S proteins by multiple alignments showed conservation of an XXXR/S motif, cleavable by either furin or other trypsin-like proteases, at a position equivalent to the second IBV furin site. Taken together, these results suggest that proteolysis at a novel XXXR/S motif in the S2 subunit might be a common mechanism for the entry of CoV into cells.
DOI: 10.1128/JVI.00613-09
PubMed: 19553314
Affiliations:
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Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Proteolytic activation of the spike protein at a novel RRRR/S motif is implicated in furin-dependent entry, syncytium formation, and infectivity of coronavirus infectious bronchitis virus in cultured cells.</title><author><name sortKey="Yamada, Yoshiyuki" sort="Yamada, Yoshiyuki" uniqKey="Yamada Y" first="Yoshiyuki" last="Yamada">Yoshiyuki Yamada</name><affiliation><nlm:affiliation>Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138673</wicri:noCountry></affiliation></author><author><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2009">2009</date><idno type="RBID">pubmed:19553314</idno><idno type="pmid">19553314</idno><idno 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of coronavirus infectious bronchitis virus in cultured cells.</title><author><name sortKey="Yamada, Yoshiyuki" sort="Yamada, Yoshiyuki" uniqKey="Yamada Y" first="Yoshiyuki" last="Yamada">Yoshiyuki Yamada</name><affiliation><nlm:affiliation>Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673.</nlm:affiliation><wicri:noCountry code="subField">Singapore 138673</wicri:noCountry></affiliation></author><author><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Substitution</term><term>Animals</term><term>Cell Fusion</term><term>Chlorocebus aethiops</term><term>Furin (metabolism)</term><term>Giant Cells (virology)</term><term>Infectious bronchitis virus (physiology)</term><term>Membrane Glycoproteins (metabolism)</term><term>Mutagenesis, Site-Directed</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Viral Envelope Proteins (metabolism)</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Cellules géantes (virologie)</term><term>Furine (métabolisme)</term><term>Fusion cellulaire</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires (métabolisme)</term><term>Motifs d'acides aminés</term><term>Mutagenèse dirigée</term><term>Protéines de l'enveloppe virale (métabolisme)</term><term>Pénétration virale</term><term>Substitution d'acide aminé</term><term>Virus de la bronchite infectieuse (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Furin</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Furine</term><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus de la bronchite infectieuse</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Infectious bronchitis virus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules géantes</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Giant Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Motifs</term><term>Amino Acid Substitution</term><term>Animals</term><term>Cell Fusion</term><term>Chlorocebus aethiops</term><term>Mutagenesis, Site-Directed</term><term>Spike Glycoprotein, Coronavirus</term><term>Vero Cells</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Fusion cellulaire</term><term>Glycoprotéine de spicule des coronavirus</term><term>Motifs d'acides aminés</term><term>Mutagenèse dirigée</term><term>Pénétration virale</term><term>Substitution d'acide aminé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The spike (S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR(537)/S in virus-infected cells. In this study, we observe that the S2 subunit of the IBV Beaudette strain is additionally cleaved at the second furin site (RRRR(690)/S) in cells expressing S constructs and in virus-infected cells. Detailed time course experiments showed that a peptide furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, blocked both viral entry and syncytium formation. Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry. Instead, a yet-to-be-identified serine protease(s) was involved, as revealed by protease inhibitor studies. Furthermore, sequence analysis of CoV S proteins by multiple alignments showed conservation of an XXXR/S motif, cleavable by either furin or other trypsin-like proteases, at a position equivalent to the second IBV furin site. Taken together, these results suggest that proteolysis at a novel XXXR/S motif in the S2 subunit might be a common mechanism for the entry of CoV into cells.</div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Liu, Ding Xiang" sort="Liu, Ding Xiang" uniqKey="Liu D" first="Ding Xiang" last="Liu">Ding Xiang Liu</name><name sortKey="Yamada, Yoshiyuki" sort="Yamada, Yoshiyuki" uniqKey="Yamada Y" first="Yoshiyuki" last="Yamada">Yoshiyuki Yamada</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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