Antiviral factor AID/APOBECs and Hepatitis B virus-related hepatocellular carcinogenesis

抗病毒因子AID/APOBECs与乙型肝炎病毒相关的肝细胞癌变

• 批准号: 23790780
• 负责人: KITAMURA Kouichi
• 金额: $ 2.66万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790780/
• 关键词: ウイルス; がん; B型肝炎

Recent studies have revealed that AID/APOBEC cytidine deaminase family members can induce C-to-U hypermutation on viral genome and restrict replication of various types of virus including HBV. Uracil residues in DNA are removed by base excision repair (BER) enzyme, uracil DNA glycosylase (UNG) when cytidine deamination is occurred in host genome.Here, we investigated whether uracil residues were removed by UNG from HBV and DHBV DNAs using in vitro cell culture system. When UNG activity was inhibited by the expression of UNG inhibitory protein (UGI), the APOBEC3G-mediated hypermutation of HBV nucleocapsid DNA was enhanced. The enhanced hypermutation by APOBEC3G and UGI was also observed in DHBV cccDNA, which was more frequent than in nucleocapsid DNA. We also found that overexpression of chicken AID caused hypermutation and reduction of DHBV cccDNA levels. These results indicate that UNG excises uracils from viral genome deaminated by AID/APOBEC protein during or after cccDNA formation.

近年来的研究发现AID/APOBEC胞苷脱氨酶家族成员可诱导病毒基因组的C → U超突变，限制包括HBV在内的多种病毒的复制。当宿主基因组发生胞苷脱氨反应时，尿嘧啶DNA糖基化酶（Uracil DNA glycosylase，UNG）可以去除DNA中的尿嘧啶残基，本研究利用体外细胞培养系统研究了UNG是否可以去除HBV和DHBV DNA中的尿嘧啶残基。当UNG抑制蛋白（UGI）的表达抑制UNG活性时，APOBEC 3G介导的HBV核衣壳DNA超突变增强。在DHBV cccDNA中也观察到APOBEC 3G和UGI增强的超突变，这比核衣壳DNA更频繁。我们还发现过表达鸡AID导致DHBV cccDNA水平的高突变和降低。这些结果表明，UNG在cccDNA形成期间或之后从病毒基因组中切除被AID/APOBEC蛋白脱氨基的尿嘧啶。

项目成果

B型肝炎ウイルスcccDNAに対する脱アミノ化酵素AIDの作用

脱氨酶AID对乙型肝炎病毒cccDNA的影响

• 发表时间: 2013
• 作者: Wakai T;Shirai Y;Sakata J;Korita PV;Matsuda Y;Takamura M;Ohashi R;Nagahashi M;Ajioka Y;Hatakeyama K;喜多村晃一
• 通讯作者: 喜多村晃一

Uracil DNA glycosylase counteracts APOBEC3G-induced hypermutation of hepatitis B viral genomes: excision repair of covalently closed circular DNA.

• DOI: 10.1371/journal.ppat.1003361
• 发表时间: 2013
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Kitamura K;Wang Z;Chowdhury S;Simadu M;Koura M;Muramatsu M
• 通讯作者: Muramatsu M

Activation-induced cytidine deaminase and base excision pathway induced hepadnavirus cccDNA degradation

激活诱导的胞苷脱氨酶和碱基切除途径诱导嗜肝DNA病毒cccDNA降解

• 作者: 栗山茂;金岡繁;濱屋寧;杉本光繁;杉本健;大澤恵;伊熊睦博;後藤修ら;栗山茂;Sajeda Chowdhury
• 通讯作者: Sajeda Chowdhury

Base Excision Repair Pathway in Hypermutated Hepatitis B virus Genome高頻度突然変異を受けたB型肝炎ウイルスゲノムにおける塩基除去修復機構

超突变乙型肝炎病毒基因组中的碱基切除修复途径 超突变乙型肝炎病毒基因组中的碱基切除修复机制

• 发表时间: 2011
• 作者: 櫻井幸,中川美奈,坂本直哉;Kitamura K;Kitamura K;東正新,坂本直哉,櫻井幸,吉野耕平,幾世橋佳,新田沙由梨,北詰晶子,村川美也子,中川美奈,柿沼晴,渡辺守;Kitmaura K
• 通讯作者: Kitmaura K

Uracil Excision Repair Pathway in APOBEC3G-edited Hepatitis B virus Genome

APOBEC3G 编辑的乙型肝炎病毒基因组中的尿嘧啶切除修复途径

• 发表时间: 2011
• 作者: Kouichi Kitamura;Zhe Wang;Sajeda Chowdhury;Miyuki Simadu;Miki Koura;and Masamichi Muramatsu
• 通讯作者: and Masamichi Muramatsu