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

doi:doi:10.1038/sj.gene.6364378

Genes and Immunity (2007) 8, 224–231. doi:10.1038/sj.gene.6364378; published online 1 March 2007

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

W Shao¹, J Tang², W Song¹, C Wang¹, Y Li², C M Wilson^2,3 and R A Kaslow^1,2

¹Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
²Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
³Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: Professor RA Kaslow or Dr J Tang, Program in Epidemiology of Infection and Immunity, Schools of Medicine and Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294-0022, USA. E-mail: rkaslow@uab.edu or jtang@uab.edu

Received 9 October 2006; Revised 21 January 2007; Accepted 22 January 2007; Published online 1 March 2007.

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Abstract

As members of the chemokine family, macrophage inflammatory protein 1 alpha (MIP-1) and MIP-1 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 and MIP-1 (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.