Characterization of the interaction between hepatitis C virus NS5B and the human oestrogen receptor alpha
Characterization of the interaction between hepatitis C virus NS5B and the human oestrogen receptor alpha
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DOI：
10.1099/vir.0.039396-0
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发表时间：
2012-04-01
影响因子：
3.8
通讯作者：
Mas, Antonio
中科院分区：
文献类型：
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作者：
Hillung, Julia;Ruiz-Lopez, Elena;Mas, Antonio
丙型肝炎病毒（HCV）的RNA依赖性RNA聚合酶（NS 5 B）是病毒复制复合体的一部分，在HCV复制中起着至关重要的作用。已经描述了NS 5 B与细胞蛋白质相互作用，并且NS 5 B与宿主蛋白质之间的相互作用对于病毒复制至关重要。参与HCV复制周期的一些宿主因子包括雌激素受体α（ESR 1）、蛋白激酶（c-Src）和分子伴侣（Hsp 70）。在这份报告中，我们确定了NS 5 B和结构域C的ESR 1（ESR 1C）之间的相互作用的要求，通过使用福斯特共振能量转移。NS 5 B-ESR 1C和ESR 1C-ESR 1C相互作用依赖于离子强度，表明接触主要是静电的。此外，参与NS 5 B寡聚化的NS 5 B残基也是NS 5 B-ESR 1C相互作用所必需的。研究病毒与宿主因子之间的相互作用将为建立创新的治疗策略和开发新的抗病毒药物提供数据。
The RNA-dependent RNA polymerase (NS5B) of hepatitis C virus (HCV) is part of the viral replicative complex and plays a crucial role in HCV replication. It has been described that NS5B interacts with cellular proteins, and that interactions between NS5B and host proteins are crucial for viral replication. Some of the host factors involved in the HCV replication cycle include the oestrogen receptor alpha (ESR1), protein kinases (c-Src) and chaperones (Hsp70). In this report, we determine the requirements for the interplay between NS5B and the domain C of ESR1 (ESR1C) by using Forster Resonance Energy Transfer. NS5B-ESR1C and ESR1C-ESR1C interactions are dependent on ionic strength, indicating that contacts are mainly electrostatic. Additionally, NS5B residues involved in NS5B oligomerization were also essential for NS5B-ESR1C interaction. The study of the interactions among viral and host factors will provide data to establish innovative therapeutic strategies and the development of new antiviral drugs.