Department of Environmental and Occupational Health, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Department of Biopharmaceutics, Air Force Military Medical University, Xi'an, Shaanxi, China.
J Med Virol. 2020 Jan;92(1):53-61. doi: 10.1002/jmv.25572. Epub 2019 Aug 29.
Hepatitis B virus (HBV) DNA is vulnerable to editing by human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases. However, the distribution of APOBEC-induced mutations on HBV DNA is not well characterized. To this end, we obtained the HBV DNA sequence of HBV-infected individuals with and without hepatocellular carcinoma (HCC and non-HCC groups, respectively) from NCBI database and calculated the r values of APOBEC-induced TpCpW→TpKpW mutation prevalence in HBV DNA. The results showed that the APOBEC-induced mutations were mainly distributed in the minus strand of non-HCC-derived HBV DNA (r = 2.04), while the mutation on the plus-strand was weaker (r = 0.99). There were high APOBEC-induced mutation regions in the minus strand of HBV DNA 1 to 1000 nucleotides (nts) region and in the plus-strand of HBV DNA 1000 to 1500 nts region; the mutations in the 1 to 1000 nts region were mainly TpCpW→TpTpW mutation types (total T/G: 111/18) and a number of these were missense mutations (missense/synonymous: 35/94 in P gene, 17/15 in S gene, and 5/10 in X gene). The difference between minus to plus-strand r of HCC-derived HBV DNA (1.96) was greater than that of the non-HCC group (1.05). The minus-strand r of HCC-derived HBV DNA regions 1000 to1500nts and 1500 to 2000 nts (r = 4.2 and 4.2) was also higher than that of the same regions of non-HCC-derived HBV DNA (r = 1.2 and 1.1). Finally, the ratio of minus to plus-strand r was used to distinguish HCC-derived HBV DNA from non-HCC-derived HBV DNA. This study unraveled the distribution characteristics of APOBEC-induced mutations on double strands of HBV DNA from HCC and non-HCC samples. Our findings would help understand the mechanism of APOBECs on HBV DNA and may provide important insights for the screening of HCC.
乙型肝炎病毒 (HBV) DNA 易受人类载脂蛋白 B mRNA 编辑酶、催化多肽样 (APOBEC) 胞嘧啶脱氨酶的编辑。然而，HBV DNA 上 APOBEC 诱导突变的分布尚不清楚。为此，我们从 NCBI 数据库中获得了乙型肝炎病毒感染个体的 HBV DNA 序列，这些个体患有肝细胞癌 (HCC 和非 HCC 组)，并计算了 HBV DNA 中 APOBEC 诱导的 TpCpW→TpKpW 突变流行率的 r 值。结果表明，APOBEC 诱导的突变主要分布在非 HCC 衍生的 HBV DNA 的负链上 (r = 2.04)，而正链上的突变较弱 (r = 0.99)。HBV DNA 1 至 1000 个核苷酸 (nts) 区域的负链和 HBV DNA 1000 至 1500 nts 区域的正链上存在高 APOBEC 诱导突变区域；1 至 1000 nts 区域的突变主要为 TpCpW→TpTpW 突变类型(总 T/G：111/18)，其中许多为错义突变(错义/同义：P 基因 35/94，S 基因 17/15，X 基因 5/10)。HCC 衍生的 HBV DNA 负链与正链 r 值的差异(1.96)大于非 HCC 组(1.05)。HCC 衍生的 HBV DNA 1000 至 1500 nts 和 1500 至 2000 nts 区域的负链 r 值(4.2 和 4.2)也高于非 HCC 衍生的 HBV DNA 的相同区域(r = 1.2 和 1.1)。最后，用负链与正链 r 值的比值来区分 HCC 衍生的 HBV DNA 和非 HCC 衍生的 HBV DNA。本研究揭示了 HCC 和非 HCC 样本中 HBV DNA 双链上 APOBEC 诱导突变的分布特征。我们的研究结果有助于理解 APOBEC 对 HBV DNA 的作用机制，并可能为 HCC 的筛查提供重要线索。
