Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.

Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.
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DOI:
10.1099/jgv.0.000663
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发表时间:
2017-03
期刊:
The Journal of general virology
影响因子:
--
通讯作者:
Sasaki T
Sasaki T
中科院分区:
其他
文献类型:
--
作者:
Tanaka Y;Sato Y;Sasaki T

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猫冠状病毒(FCoV)导致致命的疾病猫传染性腹膜炎,这是目前无法治愈的药物治疗,也没有有效的疫苗。环孢菌素A(CsA)是一种亲环素(Cyp)抑制剂,在体外和体内抑制FCoV的复制以及人和动物冠状病毒的复制。然而,CsA调节冠状病毒复制的机制尚不清楚。在这项研究中,我们分析了Cyps在FCoV复制中的作用,使用对Cyps特异性的敲除和敲除细胞。CypA和CypB的抑制减少了FCoV的复制,敲除细胞中的复制比敲低细胞中的复制少得多。此外,由CypA和CypB表达的蛋白在其各自预测的肽基脯氨酰顺式异构酶活性位点中具有突变,这也改变了Cyps和CsA之间的亲和力,抑制了FCoV复制。这些结果表明,肽基脯氨酰顺式异构酶的Cyps的活性位点可能需要FCoV复制。
Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis–transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis–transisomerase active sites of Cyps might be required for FCoV replication.
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