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J Virol, April 1998, p. 3464-3468, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Alanine Substitutions of Polar and Nonpolar Residues in the Amino-Terminal Domain of CCR5 Differently Impair Entry of Macrophage- and Dualtropic Isolates of Human Immunodeficiency Virus Type 1

Gwénaël E. E. Rabut, Jason A. Konner, Francis Kajumo, John P. Moore, and Tatjana Dragic*

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016

Received 8 October 1997/Accepted 15 December 1997

Multiple extracellular domains of the CC-chemokine receptor CCR5 are important for its function as a human immunodeficiency virus type 1 (HIV-1) coreceptor. We have recently demonstrated by alanine scanning mutagenesis that the negatively charged residues in the CCR5 amino-terminal domain are essential for gp120 binding and coreceptor function. We have now extended our analysis of this domain to include most polar and nonpolar amino acids. Replacement of alanine with all four tyrosine residues and with serine-17 and cysteine-20 decrease or abolish gp120 binding and CCR5 coreceptor activity. Tyrosine-15 is essential for viral entry irrespective of the test isolate. Substitutions at some of the other positions impair the entry of dualtropic HIV-1 isolates more than that of macrophagetropic ones.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, 455 1st Ave., 7th floor, New York, NY 10016. Phone: (212) 448-5053. Fax: (212) 725-1126. E-mail: tdragic{at}adarc.org.




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