Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.

<h4>Background</h4>Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns o...

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Autores principales:	Jean Kaoru Millet, François Kien, Chung-Yan Cheung, Yu-Lam Siu, Wing-Lim Chan, Huiying Li, Hiu-Lan Leung, Martial Jaume, Roberto Bruzzone, Joseph S Malik Peiris, Ralf Marius Altmeyer, Béatrice Nal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06b9d55ced654719b4caa76f17b3525a
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spelling	oai:doaj.org-article:06b9d55ced654719b4caa76f17b3525a2021-11-18T08:07:58ZEzrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.1932-620310.1371/journal.pone.0049566https://doaj.org/article/06b9d55ced654719b4caa76f17b3525a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23185364/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process.<h4>Methodology/principal findings</h4>We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion.<h4>Conclusions/significance</h4>Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.Jean Kaoru MilletFrançois KienChung-Yan CheungYu-Lam SiuWing-Lim ChanHuiying LiHiu-Lan LeungMartial JaumeRoberto BruzzoneJoseph S Malik PeirisRalf Marius AltmeyerBéatrice NalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49566 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jean Kaoru Millet François Kien Chung-Yan Cheung Yu-Lam Siu Wing-Lim Chan Huiying Li Hiu-Lan Leung Martial Jaume Roberto Bruzzone Joseph S Malik Peiris Ralf Marius Altmeyer Béatrice Nal Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
description	<h4>Background</h4>Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process.<h4>Methodology/principal findings</h4>We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion.<h4>Conclusions/significance</h4>Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.
format	article
author	Jean Kaoru Millet François Kien Chung-Yan Cheung Yu-Lam Siu Wing-Lim Chan Huiying Li Hiu-Lan Leung Martial Jaume Roberto Bruzzone Joseph S Malik Peiris Ralf Marius Altmeyer Béatrice Nal
author_facet	Jean Kaoru Millet François Kien Chung-Yan Cheung Yu-Lam Siu Wing-Lim Chan Huiying Li Hiu-Lan Leung Martial Jaume Roberto Bruzzone Joseph S Malik Peiris Ralf Marius Altmeyer Béatrice Nal
author_sort	Jean Kaoru Millet
title	Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
title_short	Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
title_full	Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
title_fullStr	Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
title_full_unstemmed	Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.
title_sort	ezrin interacts with the sars coronavirus spike protein and restrains infection at the entry stage.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/06b9d55ced654719b4caa76f17b3525a
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Ezrin interacts with the SARS coronavirus Spike protein and restrains infection at the entry stage.

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