Association of anti-hepatitis B virus pathway with carcinogenesis

据报道，人APOBEC3蛋白是一种抗病毒因子，通过胞嘧啶脱氨作用催化乙肝病毒DNA上的C-U转化。从表达APOBEC3G的肝癌细胞中观察到HBVDNA正链上广泛的G-to-A超突变。我们调查了UNG是否也处理具有碱基切除活性的高突变的乙肝病毒基因组。我们发现UNG抑制导致核内cccDNA高度突变的积累和细胞质rcDNA水平的降低。测序分析表明，其中一些cccDNA突变导致病毒聚合酶编码区的无义密码子。这些结果表明，核UNG触发的BER通路修复了由抗病毒APOBECs引入的病毒DNA突变。

Human APOBEC3 proteins are reported to be antiviral factors and catalyze C-to-U conversion on hepatitis B virus (HBV) DNA by cytosine deamination. Extensive G-to-A hypermutation on plus-strand of HBV DNA has been observed from APOBEC3G-expressing hepatoma cells. We investigated whether UNG also process the hypermutated HBV genome with base excision activity. We found that the UNG inhibition caused accumulation of hypermutation in nuclear cccDNA and decrease of cytoplasmic rcDNA level. Sequencing analysis showed that some of these cccDNA mutations resulted in nonsense codons within viral polymerase coding region. These results suggest that the BER pathway triggered from nuclear UNG repairs the viral DNA mutations introduced by the antiviral APOBECs.