Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity
Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity
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DOI：
10.1128/jvi.01647-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Nichol, Stuart T.
中科院分区：
文献类型：
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作者：
Bergeron, Eric;Vincent, Martin J.;Nichol, Stuart T.
克里米亚-刚果出血热病毒（CCHFV）引起严重的人类疾病。CCHFV培养基RNA编码一种多蛋白，该多蛋白经过蛋白水解加工后产生糖蛋白前体PreGn和PreGc，然后是结构糖蛋白Gn和Gc。枯草杆菌激酶同工酶-1/位点-1蛋白酶（SKI-1/SIP）在Gn加工中起核心作用。本研究表明，缺乏SKI-1/SIP的cchfv感染细胞不产生感染性病毒，尽管preg和PreGc在病毒组装部位高尔基体中正常积累。只分泌缺乏病毒糖蛋白（Gn/Ge或PreGn/PreGc）的含核蛋白颗粒。SKI-1/ slp缺陷细胞与SKI-1/SIP表达载体的互补恢复了感染性病毒的释放（bbb10 (6) PFU/ml），证实了病毒糖蛋白的整合需要SKI-1/SIP加工。SKI-1/SIP可能是一个有希望的抗病毒靶点。
Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe human disease. The CCHFV medium RNA encodes a polyprotein which is proteolytically processed to yield the glycoprotein precursors PreGn and PreGc, followed by structural glycoproteins Gn and Gc. Subtilisin kexin isozyme-1/site-1 protease (SKI-1/SIP) plays a central role in Gn processing. Here we show that CCHFV-infected cells deficient in SKI-1/SIP produce no infectious virus, although PreGn and PreGc accumulated normally in the Golgi apparatus, the site of virus assembly. Only nucleoprotein-containing particles which lacked virus glycoproteins (Gn/Ge or PreGn/PreGc) were secreted. Complementation of SKI-1/SlP-deficient cells with a SKI-1/SIP expression vector restored release of infectious virus (> 10(6) PFU/ml), confirming that SKI-1/SIP processing is required for incorporation of viral glycoproteins. SKI-1/SIP may represent a promising antiviral target.