title: Fumagillin suppresses HIV-1 infection of macrophages through the inhibition of Vpr activity.
abstract: HIV-1 viral protein R (Vpr) is one of the human immunodeficiency virus type 1 encoded proteins that have important roles in viral pathogenesis. However, no clinical drug for AIDS therapy that targets Vpr has been developed. Here, we have established a screening system to isolate Vpr inhibitors using budding yeast cells. We purified a Vpr inhibitory compound from fungal metabolites and identified it as fumagillin, a chemical already known to be a potent inhibitor of angiogenesis. Fumagillin not only reversed the growth inhibitory activity of Vpr in yeast and human cells, but also inhibited Vpr-dependent viral gene expression upon the infection of human macrophages.
authors.affiliation: Antibiotics Laboratory, Discovery Research Institute, RIKEN, 2-1, Hirosawa, Wako, 351-0198, Japan. nwatanab@riken.jp
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishihara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D003510:Cyclohexanes; D004353:Drug Evaluation, Preclinical; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016336:Gene Products, vpr / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D008666:Metalloendopeptidases / Q000378:metabolism; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects; D012717:Sesquiterpenes; D015398:Signal Transduction / Q000187:drug effects; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D016336:Gene Products, vpr; D012717:Sesquiterpenes; D054325:vpr Gene Products, Human Immunodeficiency Virus; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases