HCV在野生型人肝细胞瘤Huh-7细胞中复制效率低，但能在某些Huh-7细胞亚克隆中大量复制。我们在前面的研究中证明抑制HCV复制的细胞转录因子cAMP 应答原件结合蛋白3样因子1的沉默允许HCV在Huh7细胞亚克隆HRP1细胞中的复制。干扰素诱导抗病毒基因MX1沉默可以使另一个Huh-7亚克隆HRP4细胞支持HCV复制。通过DNA甲基化分别在HRP1和HRP4细胞中使CREB3L1和MX1沉默。我们进一步证明Huh-7细胞是各种类型基因甲基化的混合种群，HCV可以在利用DNA高甲基化使抗病毒基因沉默的细胞亚群中复制。我们的结果证明理解Huh-7细胞亚克隆允许HCV复制的机制对于研究其与HCV相互作用是必要的。

吉林大学第一医院肝胆胰内科 齐月 摘译

本文首次发表于[J Virol. 2012 Oct 31]

Epigenetic Silencing of Antiviral Genes Renders Clones of Huh-7 Cells Permissive for Hepatitis C Virus Replication

Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cAMP response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of Myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for  HRP4 cells, another subclone of Huh-7 cells, to be permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation, and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.点击下载此文件