- 作者: Woan-Eng Chan; Steve S.-L. Chen
- 作者服務機構: Institute of Biomedical Sciences, Academia S璯ica, No. 128 Yen-Chiu-Yuan Road, Section 2, Nankang, Taipei, 11529, Taiwan, ROC
- 中文摘要: --
- 英文摘要: We previously described a novel mode of downregulation of human immunodeficiency virus type 1 (HTV-1) Gag expression by a cytoplasmic domain fusion protein of the envelope (Env) transmembrane protein, β-galactosidase (β-gal)/706-856, which contains the cytoplasmic tail of gp41 fused at the C terminus of Escherichia coli β-gal. In the present study, we showed that this mediator conferred a dose-dependent dominant interference with virus infectivity. In the context of an HIV-1 provirus, this inhibitor down-regulated steady-state Env expression. Paradoxically, Env overexpression suppressed β-gal/706-856-me-diatd Gag downregulation. Sucrose gradient ultracentrifugation and confocal microscopy revealed that Gag, Env, and β-gal/706-856 had stable interactions and formed aggregated complexes in perinuclear regions. Moreover, Env overexpression hindered colocalization of Gag with β-gal/706-856 in the perinuclear region. Further cytoplasmic domain mapping analyses showed a correlation between the ability of cytoplasmic subdomains to downregulate Gag expression and the ability of these subdomains to stably interact with Gag. These studies show that redirection of Gag from its cytoplasmic synthesis site to a perinuclear compartment is a prerequisite for β-gal/706-856-mediated Gag downregulation. The results also illustrate that the dynamic interplay among Gag, Env, and β-gal/706-856 can modulate Gag and Env expression, thus controlling HIV-1 infection.
- 中文關鍵字: --
- 英文關鍵字: HIV-1, gp41, cytoplasmic domain fusion protein, dominant-negative inhibition, Gag downregulation