Heterozygous defect in HIV-1 coreceptor CCR5 and chemokine production

CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus 1 (HIV-1). An inactive CCR5 allele with a 32-nucleotide deletion (CCR5 Delta 32) has been described that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. We found the allele CCR5 Delta 32 to be not rare in 399 Swiss blood donors with a frequency of 0.080. To assess the influence of defective CCR5 on production of its ligands we determined the capacity to produce the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and RANTES in comparison with the production of the CXC chemokine IL-8 which does not bind to CCR5. Production of chemokines was determined during endotoxin stimulation of whole-blood samples ex vivo. Both, basal and LPS-induced chemokine production in 32 blood donors heterozygous for CCR5 Delta 32 were not significantly different when compared with 55 blood donors who were homozygous for the wild type CCR5 allele. (C) 1999 Academic Press.