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J Biomed Sci ; 23: 14, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26801988

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV) caused a global panic due to its high morbidity and mortality during 2002 and 2003. Soon after the deadly disease outbreak, the angiotensin-converting enzyme 2 (ACE2) was identified as a functional cellular receptor in vitro and in vivo for SARS-CoV spike protein. However, ACE2 solely is not sufficient to allow host cells to become susceptible to SARS-CoV infection, and other host factors may be involved in SARS-CoV spike protein-ACE2 complex. RESULTS: A host intracellular filamentous cytoskeletal protein vimentin was identified by immunoprecipitation and LC-MS/MS analysis following chemical cross-linking on Vero E6 cells that were pre-incubated with the SARS-CoV spike protein. Moreover, flow cytometry data demonstrated an increase of the cell surface vimentin level by 16.5 % after SARS-CoV permissive Vero E6 cells were treated with SARS-CoV virus-like particles (VLPs). A direct interaction between SARS-CoV spike protein and host surface vimentin was further confirmed by far-Western blotting. In addition, antibody neutralization assay and shRNA knockdown experiments indicated a vital role of vimentin in cell binding and uptake of SARS-CoV VLPs and the viral spike protein. CONCLUSIONS: A direct interaction between vimentin and SARS-CoV spike protein during viral entry was observed. Vimentin is a putative anti-viral drug target for preventing/reducing the susceptibility to SARS-CoV infection.


Assuntos
Peptidil Dipeptidase A/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Vimentina/metabolismo , Internalização do Vírus , Enzima de Conversão de Angiotensina 2 , Animais , Chlorocebus aethiops , Peptidil Dipeptidase A/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Células Sf9 , Glicoproteína da Espícula de Coronavírus/genética , Spodoptera , Células Vero , Vimentina/genética
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