Differential effects of viroporin inhibitors against feline infectious peritonitis virus serotypes I and II.
Differential effects of viroporin inhibitors against feline infectious peritonitis virus serotypes I and II.
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DOI：
10.1007/s00705-015-2370-x
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发表时间：
2015-05
影响因子：
2.7
通讯作者：
Hohdatsu T
中科院分区：
文献类型：
--
作者：
Takano T;Nakano K;Doki T;Hohdatsu T
猫传染性腹膜炎病毒（FIP病毒：FIPV）是冠状病毒科的一种猫科冠状病毒，在野猫和家猫中引起一种名为FIP的致命疾病。冠状病毒的基因组编码一种疏水跨膜蛋白，即包膜(E)蛋白。E蛋白具有离子通道活性。具有离子通道活性的病毒蛋白统称为“病毒蛋白”。六亚甲基酰胺（HMA）是一种病毒孔蛋白抑制剂，可以抑制E蛋白的离子通道活性和几种冠状病毒的复制。然而，HMA和其他病毒蛋白抑制剂是否影响FIPV的复制尚不清楚。我们检测了HMA和其他病毒蛋白抑制剂（DIDS[4,4 ' -二硫氰酸-2,2 ' -二苯二磺酸]和金刚烷胺）对I型和II型FIPV感染的影响。HMA处理显著降低FIPV血清型菌株Black和KU-2的滴度，且呈剂量依赖性，但对FIPV血清型菌株79-1146的滴度仅略有降低。相比之下，DIDS处理使FIPV血清II型菌株79-1146的滴度呈剂量依赖性降低，但对FIPV血清I型菌株Black和KU-2的滴度仅略有降低。我们利用表达FIPV血清型I和II型E蛋白的大肠杆菌细胞，研究了E蛋白的离子通道活性在病毒血清型之间是否存在差异。没有观察到差异，这表明除了E蛋白之外，还有一种病毒蛋白影响了HMA和DIDS对FIPV血清I型和II型的作用差异。
Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus of the family Coronaviridae, causes a fatal disease called FIP in wild and domestic cat species. The genome of coronaviruses encodes a hydrophobic transmembrane protein, the envelope (E) protein. The E protein possesses ion channel activity. Viral proteins with ion channel activity are collectively termed “viroporins”. Hexamethylene amiloride (HMA), a viroporin inhibitor, can inhibit the ion channel activity of the E protein and replication of several coronaviruses. However, it is not clear whether HMA and other viroporin inhibitors affect replication of FIPV. We examined the effect of HMA and other viroporin inhibitors (DIDS [4,4′-disothiocyano-2,2′-stilbenedisulphonic acid] and amantadine) on infection by FIPV serotypes I and II. HMA treatment drastically decreased the titers of FIPV serotype I strains Black and KU-2 in a dose-dependent manner, but it only slightly decreased the titer of FIPV serotype II strain 79-1146. In contrast, DIDS treatment decreased the titer of FIPV serotype II strain 79-1146 in dose-dependent manner, but it only slightly decreased the titers of FIPV serotype I strains Black and KU-2. We investigated whether there is a difference in ion channel activity of the E protein between viral serotypes using E. coli cells expressing the E protein of FIPV serotypes I and II. No difference was observed, suggesting that a viroporin other than the E protein influences the differences in the actions of HMA and DIDS on FIPV serotypes I and II.
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DOI：
10.1016/j.bbamem.2013.07.025
发表时间：
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期刊：
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