CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection

As members of the chemokine family, macrophage inflammatory protein 1 alpha ( MIP-1 alpha) and MIP-1 beta are unique in that they both consist of non-allelic isoforms encoded by different genes, namely chemokine (C-C motif) ligand 3 (CCL3), CCL4, CCL3-like 1 (CCL3L1) and CCL4L1. The products of these genes and of CCL5 ( encoding RANTES, i.e., regulated on activation, normal T expressed and secreted) can block or interfere with human immunodeficiency virus type 1 (HIV-1) infection through competitive binding to chemokine (C-C motif) receptor 5 (CCR5). Our analyses of 411 adolescents confirmed that CCL3 and CCL4 genes occurred invariably as single copies ( two per diploid genome), whereas the copy numbers of CCL3L1 and CCL4L1 varied extensively ( 0 - 11 and 1 - 6 copies, respectively). Neither CCL3L1 nor CCL4L1 gene copy number variation showed appreciable impact on susceptibility to or control of HIV-1 infection. Within individuals, linear correlation between CCL3L1 and CCL4L1 copy numbers was moderate regardless of ethnicity ( Pearson correlation coefficients 0.63 - 0.65, P < 0.0001), suggesting that the two loci are not always within the same segmental duplication unit. Persistently low serum MIP-1 alpha and MIP-1 beta ( in the pg/ml range) compared with high CCL5 concentration (ng/ml range) implied that multi-copy genes CCL3L1 and CCL4L1 conferred little advantage in the intensity of expression among uninfected or infected adolescents.