Interferon resistance of hepatitis C virus replicon-harbouring cells is caused by functional disruption of type I interferon receptors
Interferon resistance of hepatitis C virus replicon-harbouring cells is caused by functional disruption of type I interferon receptors
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DOI：
10.1099/vir.0.81124-0
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发表时间：
2005-10-01
影响因子：
3.8
通讯作者：
Kato, N
中科院分区：
文献类型：
--
作者：
Naka, K;Takemoto, K;Kato, N
最近已经建立了具有抗干扰素（IFN）表型的丙型肝炎病毒（HCV）复制子细胞系。这些被分为两类：部分干扰素耐药和高度干扰素耐药。在此，评估了导致 HCV 复制子携带细胞的 IFN 抗性的病毒和细胞因素。结果表明，细胞因素而不是病毒因素导致了高度干扰素耐药表型。研究了干扰素信号传导相关因子遗传异常的可能性。结果，在具有高度IFN抗性表型的复制子携带细胞中发现了I型IFN受体基因（IFNAR1和IFNAR2c）的无义突变和缺失，但很少出现在表现出部分IFN抗性表型的细胞中。此外，在IFN-抗性表型、额外通过IFN-β处理获得的复制子携带细胞系中也发现了类似的遗传改变。此外，研究表明，在具有 IFNAR1 突变体的 IFN 抗性表型、复制子携带细胞中，野生型 IFNAR1 的异位表达恢复了 I 型 IFN 信号传导。
Hepatitis C virus (HCV) replicon-harbouring cell lines possessing interferon (IFN)-resistant phenotypes have recently been established. These were divided into two classes: partially IFN resistant and highly IFN resistant. Here, the viral and cellular factors contributing to the IFN resistance of HCV replicon-harbouring cells were evaluated. The results revealed that cellular factors rather than viral factors contributed to a highly IFN-resistant phenotype. The possibility of genetic abnormality of the factors involved in IFN signalling was investigated. As a result, nonsense mutations and deletions in type I IFN receptor genes (IFNAR1 and IFNAR2c) were found in replicon-harbouring cells showing a highly IFN-resistant phenotype, but rarely appeared in cells showing a partially IFN-resistant phenotype. Furthermore, similar genetic alterations were also found in IFN-resistant phenotype, replicon-harbouring cell lines obtained additionally by IFN-beta treatment. Moreover, it was shown that ectopic expression of wild-type IFNAR1 in IFN-resistant phenotype, replicon-harbouring cells possessing the IFNAR1 mutant restored type I IFN signalling.