title: Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin.
abstract: One well-characterized in vitro function of Nef is its ability to remove CD4, the human immunodeficiency virus (HIV) receptor, from the cell surface. Nef accomplishes this by accelerating the internalization and degradation of CD4. Current models propose that Nef promotes CD4 internalization via an increased association of CD4 with clathrin-coated pits (CCP). Here, we investigated the effect of a naturally occurring antiprotozoan antibiotic, ikarugamycin (IKA), on CD4 cell surface expression in human monocytic cells stably expressing HIV type 1 SF2 Nef. IKA was able to efficiently restore CD4 cell surface expression in Nef-expressing cells without affecting either CD4 synthesis or Nef expression. In addition, we demonstrate that IKA is also capable of efficiently blocking CD4 down-modulation in response to phorbol myristate acetate. Our data suggest that IKA may be an efficient and useful inhibitor of CCP-dependent endocytosis.
authors.affiliation: Genetic Therapy Inc., Gaithersburg, Maryland 20879, USA.
authors.forename: T
authors.initials: T
authors.lastname: Luo
authors.forename: B L
authors.initials: BL
authors.lastname: Fredericksen
authors.forename: K
authors.initials: K
authors.lastname: Hasumi
authors.forename: A
authors.initials: A
authors.lastname: Endo
authors.forename: J V
authors.initials: JV
authors.lastname: Garcia
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D015693:Gene Products, nef / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007769:Lactams; D009000:Monocytes / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D000900:Anti-Bacterial Agents; D015704:CD4 Antigens; D015693:Gene Products, nef; D007769:Lactams; D054311:nef Gene Products, Human Immunodeficiency Virus; C074292:ikarugamycin; D013755:Tetradecanoylphorbol Acetate