LEPTOMYCIN-B IS AN INHIBITOR OF NUCLEAR EXPORT - INHIBITION OF NUCLEOCYTOPLASMIC TRANSLOCATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) REV PROTEIN AND REV-DEPENDENT MESSENGER-RNA
B. Wolff et al., LEPTOMYCIN-B IS AN INHIBITOR OF NUCLEAR EXPORT - INHIBITION OF NUCLEOCYTOPLASMIC TRANSLOCATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) REV PROTEIN AND REV-DEPENDENT MESSENGER-RNA, Chemistry & biology, 4(2), 1997, pp. 139-147
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. Trans
location of Rev from the nucleus to the cytoplasm is essential if Rev
is to function. We wanted to identify inhibitors of this transport pro
cess because they would be potential antiviral agents. Results: The St
reptomyces metabolite, leptomycin B, and other antibiotics of the lept
omycin/kazusamycin family were identified as inhibitors of the nucleo-
cytoplasmic translocation of Rev at nanomolar concentrations. Rev-depe
ndent export of mRNA into the cytoplasm is also blocked by leptomycin
B, which inhibits Rev-dependent, but not Rev-independent gene expressi
on in a short-term transfection assay, In primary human monocytes, lep
tomycin B suppresses HIV-1 replication. Conclusions: Leptomycin B is t
he first low molecular weight inhibitor of nuclear export to be identi
fied. Although it cannot be used therapeutically, it should serve as a
valuable tool for dissecting nuclear export pathways.