Previous Article | Next Article ![]()
Journal of Virology, February 1999, p. 1645-1648, Vol. 73, No. 2
Aaron Diamond AIDS Research Center, The
Rockefeller University, New York, New York 10016
Received 15 June 1998/Accepted 2 November 1998
The human immunodeficiency virus type 1 coreceptor activity of CCR5
depends on certain polar and charged residues in its amino-terminal domain. Since studies of chimeric receptors have indicated that the
extracellular loops of CCR5 are also involved in viral fusion and
entry, we have explored the role of bulky, polar and nonpolar residues
in these regions. Selected amino acids in the three extracellular loops
were individually changed to alanines, and the coreceptor activities of
the mutant CCR5 proteins were tested in a luciferase reporter
virus-based entry assay. We found that the cysteines in the
extracellular loops of CCR5 are essential for coreceptor activity.
However, only minor (two- to threefold) effects on coreceptor function
were noted for all of the other alanine substitutions. We also
demonstrated that when the first 19 residues of the amino-terminal region were separated from the rest of CCR5, by insertion of
glycine/serine spacers between proline 19 and cysteine 20, coreceptor
function decreased. Together with our previous studies, these data
indicate that both an amino-terminal gp120-binding site and
extracellular domain geometry play a role in viral entry.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
CCR5-Mediated Human Immunodeficiency Virus Entry Depends on an
Amino-Terminal gp120-Binding Site and on the Conformational Integrity
of All Four Extracellular Domains

*
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.
Present address: Rte. de Fruence 20, CH 1618 Chalet-St-Denis, Switzerland.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|