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-1alpha) and MIP-1beta 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-1alpha and MIP-1beta (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.
Shao
W
W
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Tang
J
J
Song
W
W
Wang
C
C
Li
Y
Y
Wilson
C M
CM
Kaslow
R A
RA
D000293:Adolescent; D001483:Base Sequence; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
C515429:CCL3 protein, human; C492767:CCL3L1 protein, human; C066507:CCL4 protein, human; C492768:CCL4L1 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D017931:DNA Primers