APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription
APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription
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APOBEC3B 编辑 HBV DNA 并在逆转录过程中抑制 HBV 复制
DOI：
10.1016/j.antiviral.2017.11.006
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发表时间：
2018-01-01
影响因子：
7.6
通讯作者：
Hu, Yuan
中科院分区：
文献类型：
--
作者：
Chen, Yanmeng;Hu, Jie;Hu, Yuan
B型肝炎病毒是一种部分双链DNA病毒，通过逆转录进行复制，逆转录发生在细胞质中的病毒核心颗粒内。胞苷脱氨酶APOBEC 3B是HBV的细胞限制因子。最近，有报道APOBEC 3B可以在细胞核中编辑HBV cccDNA，导致其降解。然而，它是否以及如何在逆转录过程中编辑HBV核心相关DNA 5尚不清楚。我们的研究揭示了以下问题：首先，沉默HBV感染系统中的内源性APOBEC 3B导致HBV复制上调。第二，APOBEC 3 B可以抑制来自基因型（gt）A、B、C和D的HBV分离物的复制，如通过使用表达来自四种不同HBV基因型的分离物的质粒的转染所确定的。对于HBV抑制，APOBEC 3B介导的复制抑制主要取决于APOBEC 3B的C-末端活性位点。此外，采用HBV RNaseH缺陷型D 702 A突变体和聚合酶缺陷型YMHA突变体，我们证明了APOBEC 3B可以编辑HBV负链和正链DNA 5，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实验发现APOBEC 3B可以以RNA依赖的方式与HBV核心蛋白相互作用。我们的研究结果提供了证据，APOBEC 3B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，APOBEC 3B对HBV发挥多方面的抗病毒作用。
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 DNA5 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 DNA5, 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.