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

研究了人类免疫缺陷病毒1型(HIV-1)Gag蛋白N-肉豆蔻酰化在ACH-2细胞中的作用。经佛波酯(PMA)刺激的细胞感染HLV-1的能力可被N-肉豆蔻酰化抑制剂N-肉豆蔻酰甘氨酸二乙缩醛(N-Myr-GoA)所抑制，而肉豆蔻酰化的阻断可导致未成熟的GAG前体积聚。经PMA刺激的未经N-Myr-GoA处理的ACH-2细胞萌发的病毒颗粒呈典型的病毒表型，而经PMA刺激的ACH-2细胞经N-Myr-GoA处理后萌发的病毒颗粒呈扭曲状。在金标记的抗Gag和env的单抗的电子显微镜下，在PMA刺激的ACH-2中，Gag和env相邻检测到，而在N-Myr-GOA处理的细胞中没有检测到env。结果表明，HIV-1 Gag的肉豆蔻酰化可能与Gag的成熟和HIV-1的感染性获得有关。

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.