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

N-terminal modifications of the chemokine RANTES bind to C-C chemokine rece ptor 5 (CCR5) and block human immunodeficiency virus type 1 (HIV-1) infecti on with greater efficacy than native RANTES. Modified RANTES compounds indu ce rapid CCR5 internalization and much slower receptor reexpression than na tive 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 de rived from donors with different CCR5 gene polymorphisms. NNY-RANTES caused even more rapid receptor internalization and slower reexpression than amin ooxypentane (AOP)-RANTES. Polymorphisms in the promoter and coding regions of CCR5 significantly affected the receptor reexpression rate after exposur e of cells to NNY-RANTES. These observations may be relevant for understand ing the protective effects of different CCR5 genotypes against HIV-1 diseas e progression.