Regulation of HIV-1 restriction factor Apobec3G by mRNA export factor

mRNA输出因子对HIV-1限制因子Apobec3G的调节

• 批准号: 24659224
• 负责人: SAKAGUCHI NOBUO
• 金额: $ 2.5万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659224/
• 关键词: 免疫学; 感染; RNA

HIV-1 viruses cause the AIDS-associated disease symptoms during the long-term infection period. We found that mRNA export factor GANP is encapsidated into the virions as a host factor associated with cytidine deaminase APOBEC3G (A3G). GANP is involved in the HIV-1 mRNA export pathway under the Rev-dependent manner. GANP binds to HIV-1 genomic (g)RNA in the virion by regulating viral RNA metabolism. GANP directly interacts with A3G in T-cells, and the interaction is through a unique region of Gag protein involved in HIV-1 gRNA encapsidation. GANP efficiently promotes the A3G incorporation into the viral core and enhances the non-infectious viral production in the host. This knowledge would suggest the feasibility of developing the in-vivo vaccination procedure.

HIV-1病毒在长期感染期间会引起艾滋病相关疾病的症状。我们发现GANP作为与胞苷脱氨酶APOBEC3G(A3G)相关的宿主因子被包裹到病毒粒子中。GANP以REV依赖的方式参与HIV-1mRNA的输出途径。GANP通过调节病毒RNA代谢与病毒粒子中的HIV-1基因组(G)RNA结合。GANP在T细胞中直接与A3G相互作用，这种相互作用是通过参与HIV-1gRNA包裹的Gag蛋白的一个独特区域实现的。GANP有效地促进A3G进入病毒核心，并增强宿主中非感染性病毒的产生。这一知识将表明开发体内疫苗接种程序的可行性。

项目成果

Transgenic overexpression of G5PR that is normally augmented in centrocytes impairsthe enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice

通常在中心细胞中增强的 G5PR 转基因过表达会损害高亲和力抗原特异性 B 细胞的富集，增加腹膜 B-1a 细胞，并诱导老年雌性小鼠的自身免疫

• DOI: 10.4049/jimmunol.1102774
• 发表时间: 2012
• 期刊: J. Immunol
• 作者: hi H;Ohtsuji M;Tsurui H;Hirose S;and Sakaguchi N
• 通讯作者: and Sakaguchi N

Protein phosphatase subunit G5PR regulates the plasma blast differentiation and autoantibody production of peritoneal B-1a cells

蛋白磷酸酶亚基 G5PR 调节腹膜 B-1a 细胞的浆母细胞分化和自身抗体产生

• 发表时间: 2013
• 作者: Kitabatake;M.;Zhang;T. L.;Kuwahara K.;Sakaguchi;N.
• 通讯作者: N.

Mammalian TREX-2 component GANP is involved in HIV-1 mRNA export

哺乳动物 TREX-2 成分 GANP 参与 HIV-1 mRNA 输出

• 发表时间: 2012
• 作者: Maeda K;Almofty SA;Singh SK;Eid MMA;Shimoda M;Ikeda T;Shida H;Koito A;Pham P;Goodman MF;Sakaguchi N.
• 通讯作者: Sakaguchi N.

GANPを介したAPOBEC3Gの抗HIV感染阻止機構の解析

GANP介导的APOBEC3G抗HIV感染抑制机制分析

• 发表时间: 2012
• 作者: 前田和彦、Almofty SA;Singh SK;Eid MMA,下田真唯子,池田輝政、小糸厚、坂口薫雄
• 通讯作者: Eid MMA,下田真唯子,池田輝政、小糸厚、坂口薫雄

GANP regulates transcription and nucleosome occupancy at the immunoglobulin variable region for AID-accession

GANP 调节免疫球蛋白可变区的转录和核小体占据，以实现 AID 加入

• 发表时间: 2013
• 作者: Maeda K;Singh SK;Eid MMA;Almofty SA;Sakaguchi N.
• 通讯作者: Sakaguchi N.