Human immunodeficiency virus type 1 Nef-induced CD4 cell surface downregulation is inhibited by ikarugamycin

One well-characterized in vitro function of Nef is its ability to remove CD 4, the human immunodeficiency virus (HIV) receptor, from the cell surface. Nef accomplishes this by accelerating the internalization and degradation o f CD4. Current models propose that Nef promotes CD4 internalization via an increased association of CD4 with clathrin-coated pits (CCP), Here, we inve stigated the effect of a naturally occurring antiprotozoan antibiotic, ikar ugamycin (IKA), on CD4 cell surface expression in human monocytic cells sta bly expressing HIV type 1 SF2 Nef. IKA was able to efficiently restore CD4 cell surface expression in Nef-expressing cells without affecting either CD 4 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 usefu l inhibitor of CCP-dependent endocytosis.