Donor- and ligand-dependent differences in C-C chemokine receptor 5 reexpression.

Abstract:

: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.

journal_name

J Virol

journal_title

Journal of virology

authors

Sabbe R,Picchio GR,Pastore C,Chaloin O,Hartley O,Offord R,Mosier DE

doi

10.1128/JVI.75.2.661-671.2001

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

661-71

issue

2

eissn

0022-538X

issn

1098-5514

journal_volume

75

pub_type

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