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The cholesterol transport inhibitor U18666A inhibits type I feline coronavirus infection
Antiviral Research ( IF 7.6 ) Pub Date : 2017-08-03 , DOI: 10.1016/j.antiviral.2017.07.022
Tomomi Takano , Misaki Endoh , Hiroaki Fukatsu , Haruko Sakurada , Tomoyoshi Doki , Tsutomu Hohdatsu

Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. FCoV exists in two serotypes. Type I FCoV is the dominant serotype worldwide. Therefore, it is necessary to develop antiviral drugs against type I FCoV infection. We previously reported that type I FCoV is closely associated with cholesterol throughout the viral life cycle. In this study, we investigated whether U18666A, the cholesterol synthesis and transport inhibitor, shows antiviral effects against type I FCoV. U18666A induced cholesterol accumulation in cells and inhibited type I FCoV replication. Surprisingly, the antiviral activity of U18666A was suppressed by the histone deacetylase inhibitor (HDACi), Vorinostat. HDACi has been reported to revert U18666A-induced dysfunction of Niemann-Pick C1 (NPC1). In conclusion, these findings demonstrate that NPC1 plays an important role in type I FCoV infection. U18666A or other cholesterol transport inhibitor may be considered as the antiviral drug for the treatment of cats with FIP.



中文翻译:

胆固醇转运抑制剂U18666A抑制I型猫冠状病毒感染

猫传染性腹膜炎(FIP)是猫冠状病毒(FCoV)引起的野猫和家猫的致命疾病。FCoV有两种血清型。I型FCoV是全球主要的血清型。因此,有必要开发针对I型FCoV感染的抗病毒药物。我们先前曾报道,在整个病毒生命周期中,I型FCoV与胆固醇密切相关。在这项研究中,我们调查了胆固醇合成和转运抑制剂U18666A是否对I型FCoV表现出抗病毒作用。U18666A诱导胆固醇在细胞中蓄积并抑制I型FCoV复制。出乎意料的是,U18666A的抗病毒活性被组蛋白脱乙酰基酶抑制剂(HDACi)Vorinostat抑制。据报道,HDACi可逆转U18666A诱导的Niemann-Pick C1(NPC1)功能障碍。综上所述,这些发现表明,NPC1在I型FCoV感染中起着重要作用。U18666A或其他胆固醇转运抑制剂可被视为治疗FIP猫的抗病毒药物。

更新日期:2017-08-03
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