کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10772278 | 1050850 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS. Analysis of SARS-CoV spike glycoprotein (S) using recombinant plasmid and virus infections demonstrated that the S-precursor (proS) exists as a â¼190Â kDa endoplasmic reticulum form and a â¼210Â kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of â¼110 and â¼80Â kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the â¼80Â kDa protein. In agreement, proS processing, cytopathic effects, and viral titers were enhanced in recombinant Vero E6 cells overexpressing furin, PC7 or PC5B. The convertase inhibitor dec-RVKR-cmk significantly reduced proS cleavage and viral titers of SARS-CoV infected cells. In addition, inhibition of processing by dec-RVKR-cmk completely abrogated the virus-induced cellular cytopathicity. A fluorogenically quenched synthetic peptide encompassing Arg761 of the spike glycoprotein was efficiently cleaved by furin and the cleavage was inhibited by EDTA and dec-RVKR-cmk. Taken together, our data indicate that furin or PC-mediated processing plays a critical role in SARS-CoV spread and cytopathicity, and inhibitors of the PCs represent potential therapeutic anti-SARS-CoV agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 326, Issue 3, 21 January 2005, Pages 554-563
Journal: Biochemical and Biophysical Research Communications - Volume 326, Issue 3, 21 January 2005, Pages 554-563
نویسندگان
Eric Bergeron, Martin J. Vincent, Louise Wickham, Josée Hamelin, Ajoy Basak, Stuart T. Nichol, Michel Chrétien, Nabil G. Seidah,