Tanaka Yoshikazu, Amano Arisa, Morisaki Masateru, Sato Yuka, Sasaki Takashi
Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo 180-8602, Japan.
Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo 180-8602, Japan.
Antiviral Res. 2016 Feb;126:1-7. doi: 10.1016/j.antiviral.2015.11.013. Epub 2015 Dec 7.
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.
尽管猫冠状病毒(FCoV)会引发猫传染性腹膜炎(FIP),这是一种致命的传染病,但目前尚无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均具有肽基脯氨酰顺反异构酶(PPIase)活性。然而,与NIMA相互作用的蛋白(Pin1)是PPIases细小菌素亚家族的成员,与Cyps和FKBPs不同,它对各种信号通路至关重要。在此,我们证明了Pin1的基因沉默或敲除会导致体外FCoV复制减少。Pin1的特异性抑制剂二硫化四甲基秋兰姆抑制了FCoV复制。这些数据表明Pin1调节FCoV的传播。