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Journal of Virology, January 2001, p. 661-671, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.661-671.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Donor- and Ligand-Dependent Differences in C-C Chemokine Receptor 5 Reexpression†

Rebecca Sabbe,1 Gastón R. Picchio,1 Cristina Pastore,1 Olivier Chaloin,2 Oliver Hartley,2 Robin Offord,2 and Donald E. Mosier1,*

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037,1 and Département de Biochimie Médicale, Centre Medical Universitaire, Geneva 1228, Switzerland2

Received 16 August 2000/Accepted 25 October 2000

N-terminal modifications of the chemokine RANTES bind to C-C chemokine receptor 5 (CCR5) and block human immunodeficiency virus type 1 (HIV-1) infection with greater efficacy than native RANTES. Modified RANTES compounds induce rapid CCR5 internalization and much slower receptor reexpression than native RANTES, suggesting that receptor sequestration is one mode of anti-HIV activity. The rates of CCR5 internalization and reexpression were compared using the potent n-nonanoyl (NNY)-RANTES derivative and CD4+ T cells derived from donors with different CCR5 gene polymorphisms. NNY-RANTES caused even more rapid receptor internalization and slower reexpression than aminooxypentane (AOP)-RANTES. Polymorphisms in the promoter and coding regions of CCR5 significantly affected the receptor reexpression rate after exposure of cells to NNY-RANTES. These observations may be relevant for understanding the protective effects of different CCR5 genotypes against HIV-1 disease progression.

* Corresponding author. Mailing address: Department of Immunology, IMM7, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9121. Fax: (858) 784-9190. E-mail: dmosier{at}scripps.edu.

dagger Publication 13345-IMM from The Scripps Research Institute.

Journal of Virology, January 2001, p. 661-671, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.661-671.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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