Leptomycin B is an inhibitor of nuclear export: Inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA
Leptomycin B is an inhibitor of nuclear export: Inhibition of nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 (HIV-1) Rev protein and Rev-dependent mRNA
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DOI：
10.1016/s1074-5521(97)90257-x
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发表时间：
1997-02-01
影响因子：
--
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Wolff, B;Sanglier, JJ;Wang, Y
背景：人类免疫缺陷病毒1型(HIV-1)调节蛋白REV是未剪接和不完全剪接的病毒mRNAs出现在细胞质中从而进行病毒复制所必需的。如果REV要发挥作用，REV从细胞核到细胞质的转位是必不可少的。我们希望确定这一转运过程的抑制剂，因为它们可能是潜在的抗病毒药物。结果：在纳摩尔浓度下，链霉菌代谢物、轻霉素B和其他轻霉素/卡祖霉素家族的抗生素被鉴定为REV核浆转位的抑制剂。在原代培养的人单核细胞中，通过抑制REV依赖的基因表达而不是REV非依赖的基因表达，也能阻断REV依赖的mRNA输出到细胞质中。结论：在原代人单核细胞中，Leptomycin B可抑制HIV-1的复制。尽管它不能用于治疗，但它应该成为剖析核出口途径的宝贵工具。
Background: The human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev is required for unspliced and incompletely spliced viral mRNAs to appear in the cytoplasm and thus for viral replication. Translocation of Rev from the nucleus to the cytoplasm is essential if Rev is to function. We wanted to identify inhibitors of this transport process because they would be potential antiviral agents.Results: The Streptomyces metabolite, leptomycin B, and other antibiotics of the leptomycin/kazusamycin family were identified as inhibitors of the nucleo-cytoplasmic translocation of Rev at nanomolar concentrations. Rev-dependent export of mRNA into the cytoplasm is also blocked by leptomycin B, which inhibits Rev-dependent, but not Rev-independent gene expression in a short-term transfection assay, In primary human monocytes, leptomycin B suppresses HIV-1 replication.Conclusions: Leptomycin B is the first low molecular weight inhibitor of nuclear export to be identified. Although it cannot be used therapeutically, it should serve as a valuable tool for dissecting nuclear export pathways.