An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection.
An integrated transcriptomic and meta-analysis of hepatoma cells reveals factors that influence susceptibility to HCV infection.
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DOI：
10.1371/journal.pone.0025584
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Robertson DL
中科院分区：
文献类型：
--
作者：
MacPherson JI;Sidders B;Wieland S;Zhong J;Targett-Adams P;Lohmann V;Backes P;Delpuech-Adams O;Chisari F;Lewis M;Parkinson T;Robertson DL
丙型肝炎病毒是一个全球性的问题。为了更好地了解丙型肝炎病毒感染，研究人员采用了体外丙型肝炎病毒细胞培养(HCVcc)系统，该系统使用了Huh-7来源的肝癌细胞，这种细胞对丙型肝炎病毒感染特别敏感。为此目的，已经亚克隆了多种高度允许的细胞。此外，已经进化出对丙型肝炎病毒抗药性的Huh-7亚克隆也是可用的。然而，这些细胞对感染的易感性或抵抗力的机制尚未完全确定。为了阐明肝癌细胞对丙型肝炎病毒感染易感或抵抗的机制，我们对六种对感染具有不同程度许可的Huh-7来源细胞培养物进行了全基因组表达分析。许多代表广泛功能的基因在细胞间有不同的表达。为了重点研究，我们从丙型肝炎病毒复制酶复合体中鉴定宿主蛋白，对三个感染丙型肝炎病毒的细胞进行基因表达分析，并通过整合各种数据源对差异表达的宿主因子进行详细的分析。我们的结果表明，与肝癌细胞对丙型肝炎病毒感染易感性有关的变化与先天免疫反应、分泌的信号肽和宿主因素有关，这些因素在病毒进入和复制中起作用。这项工作确定了可能影响丙型肝炎病毒感染的已知和新的宿主因素。我们的发现建立在对丙型肝炎病毒和宿主细胞之间复杂相互作用的现有知识的基础上，这可能有助于开发新的抗病毒策略。
Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies.
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影响因子：
5.4
作者：
Bigger, CB;Guerra, B;Lanford, RE
通讯作者：
Lanford, RE
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
5.4
作者：
Ariumi, Yasuo;Kuroki, Misao;Kato, Nobuyuki
通讯作者：
Kato, Nobuyuki
影响因子：
5.4
作者：
Aizaki, Hideki;Morikawa, Kenichi;Suzuki, Tetsuro
通讯作者：
Suzuki, Tetsuro
影响因子：
5.4
作者：
Boutell, C;Canning, M;Everett, RD
通讯作者：
Everett, RD