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Journal of Virology, March 2001, p. 2488-2492, Vol. 75, No. 5
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

Tianci Luo,1 Brenda L. Fredericksen,2 Keiji Hasumi,3 Akira Endo,3 and J. Victor Garcia2,*

Genetic Therapy Inc., Gaithersburg, Maryland 208791; Department of Internal Medicine, University of Texas---Southwestern Medical Center, Dallas, Texas 753902; and Department of Applied Biological Science, Tokyo Noko University, Fuchu-shi, Tokyo 183, Japan3

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.

* 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.

Journal of Virology, March 2001, p. 2488-2492, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2488-2492.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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