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

Genes & Immunity volume 8, pages 224–231 (2007)Cite this article

Abstract

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

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Acknowledgements

This work was supported in part by Grants AI41951 (to RAK) and AI51173 (to JT) from National Institute of Allergy and Infectious Diseases. The parental study (REACH) was supported by the National Institute of Child Health and Human Development (U01 HD32830), with supplemental funding from the National Institutes on Drug Abuse, Allergy and Infectious Diseases, and Mental Health. Investigators and staff of the Adolescent Medicine HIV/AIDS Research Network (1994–2001) are listed in J Adolesc Health 2001; 29 (suppl): 5–6. We are grateful to all participants in the REACH cohort for their valuable contributions.

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Authors and Affiliations

  1. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

    W Shao, W Song, C Wang & R A Kaslow

  2. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    J Tang, Y Li, C M Wilson & R A Kaslow

  3. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA

    C M Wilson

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  1. W Shao
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  2. J Tang
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Correspondence to J Tang or R A Kaslow.

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Shao, W., Tang, J., Song, W. et al. CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection. Genes Immun 8, 224–231 (2007). https://doi.org/10.1038/sj.gene.6364378

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