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Science 21 November 1997:
Vol. 278. no. 5342, pp. 1470 - 1473
DOI: 10.1126/science.278.5342.1470
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Reports

CD4-Independent Binding of SIV gp120 to Rhesus CCR5

Kathleen A. Martin, Richard Wyatt, Michael Farzan, Hyeryun Choe, Luisa Marcon, Elizabeth Desjardins, James Robinson, Joseph Sodroski, * Craig Gerard, * Norma P. Gerard *

CCR5 and CD4 are coreceptors for immunodeficiency virus entry into target cells. The gp120 envelope glycoprotein from human immunodeficiency virus strain HIV-1(YU2) bound human CCR5 (CCR5hu) or rhesus macaque CCR5 (CCR5rh) only in the presence of CD4. The gp120 from simian immunodeficiency virus strain SIVmac239 bound CCR5rh without CD4, but CCR5hu remained CD4-dependent. The CD4-independent binding of SIVmac239 gp120 depended on a single amino acid, Asp13, in the CCR5rh amino-terminus. Thus, CCR5-binding moieties on the immunodeficiency virus envelope glycoprotein can be generated by interaction with CD4 or by direct interaction with the CCR5 amino-terminus. These results may have implications for the evolution of receptor use among lentiviruses as well as utility in the development of effective intervention.

K. A. Martin, Perlmutter Laboratory, Children's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
R. Wyatt, M. Farzan, H. Choe, E. Desjardins, Division of Human Retrovirology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
L. Marcon, Division of Human Retrovirology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA, and Institute of Microbiology, University of Padua Medical School, Padua 35121, Italy.
J. Sodroski, Division of Human Retrovirology, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, and Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
J. Robinson, Department of Pediatrics, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
C. Gerard and N. P. Gerard, Perlmutter Laboratory, Children's Hospital, Departments of Medicine and Pediatrics, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA 02115, USA.
Joseph Sodroski{at}DFCI.harvard.edu, gerard c{at}a1.tch.harvard.edu, and gerard{at}a1.tch.harvard.edu
*   To whom correspondence should be addressed. E-mail:

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