The switch for initiation of tumorigenesis and infectivity of HIV-1 : Protein N-myristoylation

HIV-1 肿瘤发生和感染性启动的开关：蛋白质 N-肉豆蔻酰化

• 批准号: 09672238
• 负责人: SHOJI Shozo
• 金额: $ 1.86万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672238/
• 关键词: HIV-1; N-Myristoylation; Bystander effect; HiIV-1

The role of the N-myristoylation of the human immunodeficiency virus type 1 (HIV- 1) gag protein in ACH-2 cells was studied. The infectivity of HLV-1 from the cells stimulated with phorbol 12-myristate 13-acetate (PMA) was suppressed by pretreatment with N-myristoyl glycinal diethylacetal (N-Myr-GOA), a potent N-myristoylation inhibitor, and the blockage of myristoylation resulted in accumulation of immature gag precursors. The viral particles which budded from the non-N-Myr-GOA-treated ACH-2 cells stimulated with PMA exhibited a typical viral phenotype, whereas those which budded from the N-Myr-GOA-treated ACH-2 cells stimulated with PMA were twisted, as observed electron microscopically. In electron microscopic analyses with gold-labeled monoclonal antibodies to gag and env, gag and env were detected adjacent to each other in the PMA-stimulated ACH-2, but no env was detected in the cells treated with N-Myr-GOA.Taken together, the results suggest that the myristoylation of HIV-1 gag seems to be responsible for both maturation of gag and acquisition of HIV-1 infectivity.

研究了 ACH-2 细胞中人类免疫缺陷病毒 1 型 (HIV-1) gag 蛋白的 N-肉豆蔻酰化的作用。用佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 刺激的细胞中的 HLV-1 感染性，可以通过用 N-肉豆蔻酰甘氨醛二乙缩醛 (N-Myr-GOA)（一种有效的 N-肉豆蔻酰化抑制剂）预处理来抑制，并且肉豆蔻酰化的阻断导致不成熟的 gag 前体的积累。电子显微镜观察到，用 PMA 刺激的未经 N-Myr-GOA 处理的 ACH-2 细胞出芽的病毒颗粒表现出典型的病毒表型，而用 PMA 刺激的 N-Myr-GOA 处理的 ACH-2 细胞出芽的病毒颗粒是扭曲的。在使用针对 gag 和 env 的金标记单克隆抗体进行电子显微镜分析时，在 PMA 刺激的 ACH-2 中检测到彼此相邻的 gag 和 env，但在用 N-Myr-GOA 处理的细胞中未检测到 env。 综上所述，结果表明 HIV-1 gag 的肉豆蔻酰化似乎负责 gag 的成熟和 HIV-1 感染性的获得。

项目成果

S.Shoji, et al.: "Blockage of N-Myristoylation of HIV-1 Gag Induces the Production of Impotent Progeny Virus" Biochem.Biophys.Res.Commun. 237. 504-511 (1997)

S.Shoji 等人：“阻断 HIV-1 Gag 的 N-肉豆蔻酰化会诱导产生无能子代病毒”Biochem.Biophys.Res.Commun。

S.Shoji,et al.: "The p2gag Peptide,AEAMSQVTNTATIM,Processed from HIV-1 Pr55gag Was Found to Be a Suicide inhibitor of HIV-1 Protease"Biochem.Biophys.Res.Commun. 241. 275-280 (1997)

S.Shoji 等人：“由 HIV-1 Pr55gag 加工而成的 p2gag 肽，AEAMSQVTNTATIM 被发现是 HIV-1 蛋白酶的自杀抑制剂”Biochem.Biophys.Res.Commun。

Shogo Misumi, Akiko Kudo, Ryuji Azuma, Mitsunori Tomonaga, Kazuchika Furuishi, and Shozo Shoji: "The p2gag peptide, AEAMSQVTNTATIM,produced from HIV-1 Pr55gag was found to be a suicide inhibitor of HIV-1 protease." Biochem.Biophys.Res.Commun.241. 275-280

Shogo Misumi、Akiko Kudo、Ryuji Azuma、Mitsunori Tomonaga、Kazuchika Furuishi 和 Shozo Shoji：“由 HIV-1 Pr55gag 产生的 p2gag 肽 AEAMSQVTNTATIM 被发现是 HIV-1 蛋白酶的自杀抑制剂。”

S. Shoji, et al.: "Blockage of N-Myristoylation of HIV-1 Gag Induced the Production of Impotent Progeny Virus" Biochem. Biophys. Res. Commun. 237. 504-511 (1997)

S. Shoji 等人：“阻断 HIV-1 Gag 的 N-肉豆蔻酰化诱导了无能子代病毒的产生”Biochem。