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Assessment of New E2 Protein Domain Interaction with PKR Protein to Control IFN Signaling
Current Proteomics ( IF 0.8 ) Pub Date : 2021-07-31 , DOI: 10.2174/1570164617999201006194657
Behzad Dehghani 1 , Tayebeh Hashempour 1 , Zahra Mousavi 1 , Zahra Hasanshahi 1 , Javad Moayedi 1 , Shahin Merat 2
Affiliation  

Introduction: Controversy exists regarding the impact of Phosphorylation Homology Domain (PePHD) of Hepatitis C Virus (HCV) E2 protein on the interruption of the antiviral signaling pathway. A mechanism by which the virus evades the antiviral effect of interferon (IFN) alpha involves protein kinase (PKR) eukaryotic Initiation Factor 2 alpha (eIF2a) PePHD. By binding to PKR, PePHD inhibits its activity and, therefore, causes the virus to evade the antiviral activity of IFN. This study aimed to clarify the inconsistency of different conclusions reached in previous studies using reliable bioinformatics tools.

Methods: Fifty-eight Iranian patients infected with HCV genotypes 1a and 3a and 58 healthy control individuals were examined. Plasma viral RNA was used to amplify and sequence the HCV E2 gene; also, HCV viral load, genotyping, IL-28B genotyping, alanine Aminotransferase (ALT), and aspartate aminotransferase (AST) test were determined. Bioinformatics tools determined the physicochemical properties, B-cell epitopes, post-modification changes, and secondary/tertiary structures, and also evaluated the interactions between E2 and PePHD regions.

Results: The results showed a new domain that is responsible for binding to PKR protein and is important to the intrigued antiviral response. Physicochemical features and post-modifications were defined, showing that E2 is highly phosphorylated and there were numerous possible disulfide bonds. Secondary and tertiary structures for E2 protein were constructed. No significant relationship between ALT and AST and treatment failure was detected.

Conclusion: Docking analysis showed a new domain in E2 protein that can be involved in the interaction between PKR and E2 protein. This finding may justify our results revealing the non-significant relationship between mutations in PePHD and treatment failure.



中文翻译:

评估新 E2 蛋白域与 PKR 蛋白的相互作用以控制 IFN 信号传导

简介:关于丙型肝炎病毒 (HCV) E2 蛋白的磷酸化同源域 (PePHD) 对阻断抗病毒信号通路的影响存在争议。病毒逃避干扰素 (IFN) α 抗病毒作用的机制涉及蛋白激酶 (PKR) 真核起始因子 2 α (eIF2a) PePHD。通过与 PKR 结合,PePHD 抑制其活性,从而使病毒逃避 IFN 的抗病毒活性。本研究旨在使用可靠的生物信息学工具澄清先前研究中得出的不同结论的不一致之处。

方法:对 58 名感染 HCV 基因型 1a 和 3a 的伊朗患者和 58 名健康对照个体进行了检查。血浆病毒RNA用于扩增和测序HCV E2基因;此外,还测定了 HCV 病毒载量、基因分型、IL-28B 基因分型、丙氨酸氨基转移酶 (ALT) 和天冬氨酸氨基转移酶 (AST) 测试。生物信息学工具确定了物理化学特性、B 细胞表位、修饰后变化和二级/三级结构,并评估了 E2 和 PePHD 区域之间的相互作用。

结果:结果显示了一个负责与 PKR 蛋白结合的新结构域,并且对引发的抗病毒反应很重要。定义了物理化学特征和后修饰,表明 E2 高度磷酸化并且存在许多可能的二硫键。构建了 E2 蛋白的二级和三级结构。未检测到 ALT 和 AST 与治疗失败之间的显着关系。

结论:对接分析显示E2蛋白中有一个新的结构域,可以参与PKR和E2蛋白之间的相互作用。这一发现可能证明我们的结果是正确的,即揭示 PePHD 突变与治疗失败之间的非显着关系。

更新日期:2021-07-31
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