Journal
JOURNAL OF VIROLOGY
Volume 75, Issue 5, Pages 2488-2492Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.75.5.2488-2492.2001
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Funding
- NIAID NIH HHS [AI33331, R01 AI033331] Funding Source: Medline
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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.
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