Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved S protein as revealed by pseudotype virus bearing cleaved S protein.
Identifieur interne : 003116 ( Main/Exploration ); précédent : 003115; suivant : 003117Entry from the cell surface of severe acute respiratory syndrome coronavirus with cleaved S protein as revealed by pseudotype virus bearing cleaved S protein.
Auteurs : Rie Watanabe [Japon] ; Shutoku Matsuyama ; Kazuya Shirato ; Masami Maejima ; Shuetsu Fukushi ; Shigeru Morikawa ; Fumihiro TaguchiSource :
- Journal of virology [ 1098-5514 ] ; 2008.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , physiology : Membrane Glycoproteins, Pancreatic Elastase, Viral Envelope Proteins.
- physiology : SARS Virus.
- virology : Endosomes.
- Cell Fusion, HeLa Cells, Humans, Spike Glycoprotein, Coronavirus.
Abstract
Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (S) protein is affected by trypsin, which induces cleavage of the S protein and activates its fusion potential. This suggests that SARS-CoV bearing a cleaved form of the S protein can enter cells directly from the cell surface without trypsin treatment. To explore this possibility, we introduced a furin-like cleavage sequence in the S protein at amino acids 798 to 801 and found that the mutated S protein was cleaved and induced cell fusion without trypsin treatment when expressed on the cell surface. Furthermore, a pseudotype virus bearing a cleaved S protein was revealed to infect cells in the presence of a lysosomotropic agent as well as a protease inhibitor, both of which are known to block SARS-CoV infection via an endosome, whereas the infection of pseudotypes with an uncleaved, wild-type S protein was blocked by these agents. A heptad repeat peptide, derived from a SARS-CoV S protein that is known to efficiently block infections from the cell surface, blocked the infection by a pseudotype with a cleaved S protein but not that with an uncleaved S protein. Those results indicate that SARS-CoV with a cleaved S protein is able to enter cells directly from the cell surface and agree with the previous observation of the protease-mediated cell surface entry of SARS-CoV.
DOI: 10.1128/JVI.01412-08
PubMed: 18786990
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is known to take an endosomal pathway for cell entry; however, it is thought to enter directly from the cell surface when a receptor-bound virion spike (S) protein is affected by trypsin, which induces cleavage of the S protein and activates its fusion potential. This suggests that SARS-CoV bearing a cleaved form of the S protein can enter cells directly from the cell surface without trypsin treatment. To explore this possibility, we introduced a furin-like cleavage sequence in the S protein at amino acids 798 to 801 and found that the mutated S protein was cleaved and induced cell fusion without trypsin treatment when expressed on the cell surface. Furthermore, a pseudotype virus bearing a cleaved S protein was revealed to infect cells in the presence of a lysosomotropic agent as well as a protease inhibitor, both of which are known to block SARS-CoV infection via an endosome, whereas the infection of pseudotypes with an uncleaved, wild-type S protein was blocked by these agents. A heptad repeat peptide, derived from a SARS-CoV S protein that is known to efficiently block infections from the cell surface, blocked the infection by a pseudotype with a cleaved S protein but not that with an uncleaved S protein. Those results indicate that SARS-CoV with a cleaved S protein is able to enter cells directly from the cell surface and agree with the previous observation of the protease-mediated cell surface entry of SARS-CoV.</div>
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<name sortKey="Maejima, Masami" sort="Maejima, Masami" uniqKey="Maejima M" first="Masami" last="Maejima">Masami Maejima</name>
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<name sortKey="Morikawa, Shigeru" sort="Morikawa, Shigeru" uniqKey="Morikawa S" first="Shigeru" last="Morikawa">Shigeru Morikawa</name>
<name sortKey="Shirato, Kazuya" sort="Shirato, Kazuya" uniqKey="Shirato K" first="Kazuya" last="Shirato">Kazuya Shirato</name>
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<country name="Japon"><region name="Région de Kantō"><name sortKey="Watanabe, Rie" sort="Watanabe, Rie" uniqKey="Watanabe R" first="Rie" last="Watanabe">Rie Watanabe</name>
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