Priel E, Showalter S D, Roberts M, Oroszlan S, Blair D G
Laboratory of Molecular Oncology, National Cancer Institute Frederick Cancer Research and Development Center, Maryland.
J Virol. 1991 Aug;65(8):4137-41. doi: 10.1128/JVI.65.8.4137-4141.1991.
Camptothecin (CPT), a topoisomerase I-specific inhibitor, was found in this study to inhibit the replication of equine infectious anemia virus (EIAV) in chronically infected CF2Th cells (designated CF2Th/EIAV). By measuring viral reverse transcriptase activity in the culture medium, we demonstrated that treatment for 1 h with noncytotoxic doses of this drug inhibited production by 32 to 52%, whereas continuous exposure to this drug resulted in an 85 to 92% inhibition. No effect on the viability or growth rate of the cells was detected in any of these treatments. Indirect immunofluorescence analysis of the CPT-treated CF2Th/EIAV cells with anti-p26 capsid protein antibodies showed 60 to 85% reduction in the immunofluorescence-positive cells following drug treatment, and radioimmunoprecipitation analysis of these cells showed a comparable decrease of the pr55gag precursor protein. These data suggest that CPT acts as an anti-EIAV agent to block virus replication in the chronically infected cells.
喜树碱(CPT)是一种特异性靶向拓扑异构酶I的抑制剂,本研究发现它能抑制慢性感染的CF2Th细胞(命名为CF2Th/EIAV)中马传染性贫血病毒(EIAV)的复制。通过检测培养基中的病毒逆转录酶活性,我们证明用无细胞毒性剂量的该药物处理1小时可使病毒产量降低32%至52%,而持续暴露于该药物则导致85%至92%的抑制率。在任何这些处理中均未检测到对细胞活力或生长速率的影响。用抗p26衣壳蛋白抗体对经CPT处理的CF2Th/EIAV细胞进行间接免疫荧光分析显示,药物处理后免疫荧光阳性细胞减少了60%至85%,对这些细胞进行放射免疫沉淀分析显示pr55gag前体蛋白也有类似程度的减少。这些数据表明CPT作为一种抗EIAV药物,可阻断慢性感染细胞中的病毒复制。