Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus.
Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus.
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普罗蛋白转化酶在严重急性呼吸综合征冠状病毒的加工和传播中的影响。
DOI：
10.1016/j.bbrc.2004.11.063
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发表时间：
2005-01-21
影响因子：
3.1
通讯作者：
Seidah NG
中科院分区：
文献类型：
--
作者：
Bergeron E;Vincent MJ;Wickham L;Hamelin J;Basak A;Nichol ST;Chrétien M;Seidah NG
严重急性呼吸综合征冠状病毒（SARS-CoV）是SARS的病原体。利用重组质粒和病毒感染对SARS-CoV刺突糖蛋白（S）的分析表明，S-前体（proS）以约190 kDa的内质网形式和约210 kDa的高尔基体修饰形式存在。ProS随后被加工成两种C-末端蛋白，分子量分别为110和180 kDa。膜结合的前蛋白转化酶（PC）弗林蛋白酶，PC 7或PC 5 B增强的生产的80 kDa的蛋白。在协议中，proS加工，细胞病变的影响，和病毒滴度增强重组Vero E6细胞过度表达弗林蛋白酶，PC 7或PC 5 B。转化酶抑制剂dec-RVKR-cmk显著降低了SARS-CoV感染细胞的proS切割和病毒滴度。此外，通过dec-RVKR-cmk抑制加工完全消除了病毒诱导的细胞病变。荧光猝灭的合成肽，包括Arg 761的刺突糖蛋白被弗林蛋白酶有效地切割和切割抑制EDTA和dec-RVKR-cmk。总之，我们的数据表明，弗林蛋白酶或PC介导的加工在SARS冠状病毒传播和细胞病变中起着关键作用，PC的抑制剂代表了潜在的治疗性抗SARS冠状病毒药物。
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 ∼190 kDa endoplasmic reticulum form and a ∼210 kDa Golgi-modified form. ProS is subsequently processed into two C-terminal proteins of ∼110 and ∼80 kDa. The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the ∼80 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.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
DOI：
10.4269/ajtmh.1967.16.339
发表时间：
1967-01-01
影响因子：
3.3
作者：
BRANDT, WE;BUESCHER, EL;HETRICK, FM
通讯作者：
HETRICK, FM
DOI：
10.1016/s0140-6736(03)13413-7
发表时间：
2003-05-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Nicholls JM;Poon LL;Lee KC;Ng WF;Lai ST;Leung CY;Chu CM;Hui PK;Mak KL;Lim W;Yan KW;Chan KH;Tsang NC;Guan Y;Yuen KY;Peiris JS
通讯作者：
Peiris JS
影响因子：
3.7
作者：
Gallagher TM;Buchmeier MJ
通讯作者：
Buchmeier MJ
影响因子：
5.4
作者：
Song, HC;Seo, MY;Han, JH
通讯作者：
Han, JH