Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus.

Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus.
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DOI:
10.1016/j.antiviral.2015.11.013
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发表时间:
2016-02
期刊:
影响因子:
7.6
通讯作者:
Sasaki T
Sasaki T
中科院分区:
医学2区
文献类型:
--
作者:
Tanaka Y;Amano A;Morisaki M;Sato Y;Sasaki T

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虽然猫冠状病毒(FCoV)引起猫传染性腹膜炎(FIP),这是一种致命的传染病,但没有有效的治疗药物或疫苗。此前,体外研究表明,环孢素(CsA)和FK506可抑制多种冠状病毒的病毒复制。CsA和FK506是临床相关免疫抑制药物的靶点,分别与细胞亲环蛋白(Cyps)或FK506结合蛋白(FKBPs)结合。Cyp和FKBP都具有肽酰脯氨酸顺式反式异构酶(PPIase)活性。然而,与NIMA (Pin1)相互作用的蛋白(Pin1)是PPIases的parvulin亚家族成员,不同于Cyps和FKBPs,对各种信号通路至关重要。在这里,我们证明了基因沉默或敲除Pin1导致体外FCoV复制减少。双五亚甲基硫脲单硫化物是一种特异性的Pin1抑制剂,可以抑制FCoV的复制。这些数据表明Pin1可以调节FCoV的传播。Pin1促进FCoV体外复制。Pin1的RNA干扰实验降低了FCoV的复制和病毒蛋白的表达。Pin1抑制剂DTM导致FCoV复制和蛋白表达的减少。敲除Pin1基因可抑制FCoV的复制和蛋白表达。
Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation. Pin1 facilitates FCoV replication in vitro. RNA interference experiments for Pin1 reduced FCoV replication and viral protein expression. The Pin1 inhibitor DTM results in the reduction of FCoV replication and protein expression. Knockout of the Pin1 gene inhibits FCoV replication and protein expression.
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