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Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands

Genes & Immunity volume 13, pages 202–205 (2012)Cite this article

A Corrigendum to this article was published on 19 July 2012

Abstract

Several CC-motif chemokine ligands (CCLs) can block HIV-1-binding sites on CC-motif chemokine receptor 5 (CCR5) and inhibit viral entry. We studied single-nucleotide polymorphisms (SNPs) in genes encoding three CCR5 ligands (CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES)) along with an adjacent gene encoding a CCR2 ligand (CCL2 (MCP-1)) to identify candidate markers for HIV-1 infection and pathogenesis. Analyses of 567 HIV-1 serodiscordant Zambian couples revealed that rs5029410C (in CCL3 intron 3) was associated with lower viral load (VL) in seroconverters, adjusted for gender and age (regression β=−0.57 log10, P=4 × 10−6). In addition, rs34171309A in CCL3 exon 3 was associated with increased risk of HIV-1 acquisition in exposed seronegatives (hazard ratio=1.52, P=0.006 when adjusted for VL of the initially seropositive partner and genital ulcer/inflammation). SNP rs34171309 encodes a conservative Glu-to-Asp substitution. Five neighboring SNPs in tight linkage disequilibrium with rs34171309 all showed similar associations with HIV-1 acquisition. How these multiple CCL3 SNPs may alter the occurrence or course of HIV-1 infection remains to be determined.

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Acknowledgements

We thank study participants, staff, interns and Project Management Group members of the Zambia-Emory HIV-1 Research Project in Lusaka, Zambia; technical staff and students at the virology laboratory at the University Teaching Hospital, Lusaka, the immunogenetics laboratory and the data analysis group in the Program in Epidemiology of Infection and Immunity at UAB School of Public Health. This study was supported primarily by the US National Institute of Allergy and Infectious Diseases, through Grants AI041951 and AI071906 to RAK, AI040951 to SA, AI064060 to EH and AI076123 to JT.

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Authors and Affiliations

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

    L Hu, W Song, I Brill, S Shrestha & R A Kaslow

  2. Rwanda-Zambia HIV-1 Research Group, Lusaka, Zambia

    J Mulenga & S Allen

  3. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

    S Allen

  4. Vaccine Research Center, Emory University, Atlanta, GA, USA

    E Hunter

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

    J Tang

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  1. L Hu
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Correspondence to R A Kaslow.

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Hu, L., Song, W., Brill, I. et al. Genetic variations and heterosexual HIV-1 infection: analysis of clustered genes encoding CC-motif chemokine ligands. Genes Immun 13, 202–205 (2012). https://doi.org/10.1038/gene.2011.70

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