Streblow D N, Kitabwalla M, Malkovsky M, Pauza C D
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53706, USA.
Virology. 1998 Jun 5;245(2):197-202. doi: 10.1006/viro.1998.9155.
The molecular chaperone cyclophilin A (Cyp A) modulates human immunodeficiency virus type 1 (HIV-1) infectivity through its interactions with Gag structural proteins. The molecular mechanism for CypA in HIV-1 replication is not known. We studied chaperone effects on Gag precursor processing using cyclosporin A (CsA) to bind CypA and prevent its interaction with p55Gag. CsA treatment inhibited p55Gag processing in extracellular virus-like particles produced from COS cells. We confirmed the effect of CsA on Gag processing by examining virions produced from CEMx174 cells infected with HIV-1LAI. Particles accumulated in the presence of CsA displayed mostly immature virion morphology and lacked condensed capsids. CsA has a direct effect on HIV-1 Gag processing that implicates CypA as having an important role in the maturation of HIV-1 particles.
分子伴侣亲环素A（Cyp A）通过与Gag结构蛋白相互作用来调节1型人类免疫缺陷病毒（HIV-1）的感染性。CypA在HIV-1复制中的分子机制尚不清楚。我们使用环孢素A（CsA）结合CypA并阻止其与p55Gag相互作用，研究了伴侣蛋白对Gag前体加工的影响。CsA处理抑制了COS细胞产生的细胞外病毒样颗粒中p55Gag的加工。我们通过检查感染HIV-1LAI的CEMx174细胞产生的病毒粒子，证实了CsA对Gag加工的影响。在CsA存在下积累的颗粒大多呈现未成熟的病毒粒子形态，并且缺乏浓缩的衣壳。CsA对HIV-1 Gag加工有直接影响，这表明CypA在HIV-1颗粒成熟中起重要作用。
