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Journal of Virology, March 2001, p. 2488-2492, Vol. 75, No. 5
Genetic Therapy Inc., Gaithersburg, Maryland
208791; Department of Internal Medicine,
University of Texas
Received 27 September 2000/Accepted 8 December 2000
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.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2488-2492.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Human Immunodeficiency Virus Type 1 Nef-Induced CD4
Cell Surface Downregulation Is Inhibited by Ikarugamycin
Southwestern Medical Center, Dallas, Texas
753902; and Department of Applied
Biological Science, Tokyo Noko University, Fuchu-shi, Tokyo 183, Japan3
*
Corresponding author. Mailing address: Department of
Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Y9.206, Dallas, TX
75390-9113. Phone: (214) 648-9970. Fax: (214) 648-0231. E-mail: Victor.Garcia{at}utsouthwestern.edu.
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