Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/7744
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dc.contributor.authorMillet, JK-
dc.contributor.authorKien, F-
dc.contributor.authorCheung, C-Y-
dc.contributor.authorSiu, Y-L-
dc.contributor.authorChan, W-L-
dc.contributor.authorLi, H-
dc.contributor.authorLeung, H-L-
dc.contributor.authorJaume, M-
dc.contributor.authorBruzzone, R-
dc.contributor.authorPeiris, JSM-
dc.contributor.authorAltmeyer, RM-
dc.contributor.authorNal, B-
dc.date.accessioned2013-12-02T15:44:27Z-
dc.date.available2013-12-02T15:44:27Z-
dc.date.issued2012-
dc.identifier.citationPLoS ONE, 7(11), e49566, 2012en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049566en
dc.identifier.urihttp://bura.brunel.ac.uk/handle/2438/7744-
dc.description© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.abstractBackground: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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.en_US
dc.description.sponsorshipThis work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes.en_US
dc.languageEnglish-
dc.language.isoenen_US
dc.publisherPublic Library of Scienceen_US
dc.subjectAcute Respiratory Syndrome coronavirus (SARS-CoV)en_US
dc.subjectImmunodeficiency virusen_US
dc.subjectAngiotensin-converting enzyme-2en_US
dc.subjectStable microtubulesen_US
dc.subjectViral envelope glycoprotein Spikeen_US
dc.subjectEzrin/Radixin/Moesin (ERM) family of proteinsen_US
dc.titleEzrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stageen_US
dc.typeArticleen_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0049566-
pubs.organisational-data/Brunel-
pubs.organisational-data/Brunel/Brunel Active Staff-
pubs.organisational-data/Brunel/Brunel Active Staff/School of Health Sciences & Social Care-
pubs.organisational-data/Brunel/Brunel Active Staff/School of Health Sciences & Social Care/Biological Sciences-
Appears in Collections:Biological Sciences
Community Health and Public Health
Dept of Life Sciences Research Papers

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