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APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription
Antiviral Research ( IF 4.5 ) Pub Date : 2017-11-10 , DOI: 10.1016/j.antiviral.2017.11.006
Yanmeng Chen , Jie Hu , Xuefei Cai , Yao Huang , Xing Zhou , Zeng Tu , Jieli Hu , John E. Tavis , Ni Tang , Ailong Huang , Yuan Hu

Hepatitis B virus is a partially double-stranded DNA virus that replicates by reverse transcription, which occurs within viral core particles in the cytoplasm. The cytidine deaminase APOBEC3B is a cellular restriction factor for HBV. Recently, it was reported that APOBEC3B can edit HBV cccDNA in the nucleus, causing its degradation. However, whether and how it can edit HBV core-associated DNAs during reverse transcription is unclear. Our studies to address this question revealed the following: First, silencing endogenous APOBEC3B in an HBV infection system lead to upregulation of HBV replication. Second, APOBEC3B can inhibit replication of HBV isolates from genotypes (gt) A, B, C, and D as determined by employing transfection of plasmids expressing isolates from four different HBV genotypes. For HBV inhibition, APOBEC3B-mediated inhibition of replication primarily depends on the C-terminal active site of APOBEC3B. In addition, employing the HBV RNaseH-deficient D702A mutant and a polymerase-deficient YMHA mutant, we demonstrated that APOBEC3B can edit both the HBV minus- and plus-strand DNAs, but not the pregenomic RNA in core particles. Furthermore, we found by co-immunoprecipitation assays that APOBEC3B can interact with HBV core protein in an RNA-dependent manner. Our results provide evidence that APOBEC3B can interact with HBV core protein and edit HBV DNAs during reverse transcription. These data suggest that APOBEC3B exerts multifaceted antiviral effects against HBV.



中文翻译:

APOBEC3B编辑HBV DNA并在逆转录过程中抑制HBV复制

乙型肝炎病毒是部分双链DNA病毒,可通过逆转录复制,并发生在细胞质的病毒核心颗粒内。胞苷脱氨酶APOBEC3B是HBV的细胞限制性因子。最近,据报道,APOBEC3B可以编辑细胞核中的HBV cccDNA,导致其降解。但是,在逆转录过程中是否以及如何编辑与HBV核心相关的DNA尚不清楚。我们针对该问题的研究揭示了以下内容:首先,使HBV感染系统中的内源性APOBEC3B沉默会导致HBV复制的上调。第二,如通过采用转染表达来自四种不同HBV基因型分离株的质粒所确定的,APOBEC3B可以抑制来自基因型(gt)A,B,C和D的HBV分离株的复制。对于HBV抑制,APOBEC3B介导的复制抑制作用主要取决于APOBEC3B的C端活性位点。此外,使用HBV RNaseH缺陷型D702A突变体和聚合酶缺陷型YMHA突变体,我们证明APOBEC3B可以编辑HBV负链和正链DNA,但不能编辑核心颗粒中的前基因组RNA。此外,我们通过免疫共沉淀分析发现,APOBEC3B可以与RNA依赖的方式与HBV核心蛋白相互作用。我们的结果提供了证据,表明APOBEC3B可以与HBV核心蛋白相互作用,并在逆转录过程中编辑HBV DNA。这些数据表明,APOBEC3B对HBV发挥了多方面的抗病毒作用。我们证明APOBEC3B可以编辑HBV负链和正链DNA,但不能编辑核心颗粒中的前基因组RNA。此外,我们通过免疫共沉淀分析发现,APOBEC3B可以与RNA依赖的方式与HBV核心蛋白相互作用。我们的结果提供了证据,表明APOBEC3B可以与HBV核心蛋白相互作用,并在逆转录过程中编辑HBV DNA。这些数据表明,APOBEC3B对HBV发挥了多方面的抗病毒作用。我们证明APOBEC3B可以编辑HBV负链和正链DNA,但不能编辑核心颗粒中的前基因组RNA。此外,我们通过免疫共沉淀分析发现,APOBEC3B可以与RNA依赖的方式与HBV核心蛋白相互作用。我们的结果提供了证据,表明APOBEC3B可以与HBV核心蛋白相互作用,并在逆转录过程中编辑HBV DNA。这些数据表明,APOBEC3B对HBV发挥了多方面的抗病毒作用。

更新日期:2017-11-10
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