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Journal of Virology, April 2001, p. 3971-3976, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3971-3976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Nef-Induced CD4 Downregulation: a Diacidic Sequence in Human Immunodeficiency Virus Type 1 Nef Does Not Function as a Protein Sorting Motif through Direct Binding to beta -COP

K. Janvier,1 H. Craig,2 S. Le Gall,3 R. Benarous,1 J. Guatelli,2 O. Schwartz,3 and S. Benichou1,*

Institut Cochin de Génétique Moléculaire, INSERM U529, Université Paris V,1 and Institut Pasteur,3 Paris, France, and Department of Medicine, University of California, San Diego Veterans Affairs Medical Center, La Jolla, California2

Received 20 November 2000/Accepted 26 January 2001

The Nef protein from the human immunodeficiency virus (HIV) induces CD4 cell surface downregulation by interfering with the endocytic machinery. It has been recently proposed that binding of HIV type 1 Nef to the beta  subunit of COPI coatomers participated in the Nef-induced CD4 downregulation through recognition of a novel diacidic motif found in the C-terminal disordered loop of Nef (V. Piguet, F. Gu, M. Foti, N. Demaurex, J. Gruenberg, J. L. Carpentier, and D. Trono, Cell 97:63-73, 1999). We have mutated the glutamate residues which formed this motif in order to document this observation. Surprisingly, mutation of the diacidic sequence of Nef did not significantly affect its ability (i) to interact with beta -COP, (ii) to downregulate CD4 cell surface expression, and (iii) to address an integral resident membrane protein containing Nef as the cytoplasmic domain to the endocytic pathway. Our results indicate that these acidic residues are not involved in the connection of Nef with the endocytic machinery through binding to beta -COP. Additional studies are thus required to characterize the residues of Nef involved in the binding to beta -COP and to evaluate the contribution of this interaction to the Nef-induced perturbations of membrane trafficking.

* Corresponding author. Mailing address: INSERM U529, ICGM, 24 Rue du Faubourg Saint-Jacques, 75014 Paris, France. Phone: (33) 1 44 41 25 67. Fax: (33) 1 44 41 23 99. E-mail: benichou{at}cochin.inserm.fr.

Journal of Virology, April 2001, p. 3971-3976, Vol. 75, No. 8
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.8.3971-3976.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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