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Host CCL3L1 Gene Copy Number in Relation to HIV-1-Specific CD4+ and CD8+ T-Cell Responses and Viral Load in South African Women

Shalekoff, Sharon PhD*; Meddows-Taylor, Stephen PhD*; Schramm, Diana B PhD*; Donninger, Samantha L BScHons*; Gray, Glenda E MD; Sherman, Gayle G MD, PhD; Coovadia, Ashraf H MD§; Kuhn, Louise PhD; Tiemessen, Caroline T PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2008 - Volume 48 - Issue 3 - p 245-254
doi: 10.1097/QAI.0b013e31816fdc77
Basic Science

HIV-specific T-cell responses play an important role in control of infection. Because CCL3 has immune modulatory and antiviral activities, we hypothesized that host CCL3 genotype (CCL3L1 gene duplications) would influence the development of effective HIV-specific immune responses. Copy numbers of CCL3L1 were determined for 71 HIV-infected women, and HIV-specific CD4+ and CD8+ T-cell responses to overlapping peptide pools spanning the HIV-1 subtype C genome were simultaneously measured by an interferon-γ and interleukin-2 whole-blood flow cytometric assay. Host CCL3L1 copy number correlated negatively with viral load (r = −0.239, P = 0.045), as did magnitudes of Gag CD4+ (r = −0.362, P = 0.002) and CD8+ (r = −0.261, P = 0.028) T-cell responses. Patients with a Gag CD4+ response (P = 0.002) or dominant Gag CD8+ (P = 0.006) response had significantly lower viral loads than those whose dominant response targeted another region of the genome, whereas a dominant Nef-specific CD8+ T-cell response was associated with higher HIV viral load. CCL3L1 copy number greater than or equal to the population median of 5 was significantly associated with increased magnitude of CD4+ Gag responses (P = 0.017), and women who had CD4+ and CD8+ Gag-specific responses had significantly lower viral loads (P = 0.004) and higher CCL3L1 copy number (P = 0.015) than those women with only CD8+ Gag-specific responses.

From the *AIDS Virus Research Unit, National Institute for Communicable Diseases, and University of the Witwatersrand, Johannesburg, South Africa; †Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa; ‡National Health Laboratory Services and Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa; §Coronation Hospital, Wits Paediatric HIV Working Group, Johannesburg, South Africa; and the ∥Gertrude H. Sergievsky Centre, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.

Received for publication November 27, 2007; accepted February 21, 2008.

Supported in part by the South African AIDS Vaccine Initiative and by grants from the National Institute of Child Health and Human Development (grant 42402) and the Wellcome Trust. C. T. Tiemessen is a Wellcome Trust International Senior Research Fellow (076352/Z/05/Z).

Correspondence to: Caroline T. Tiemessen, PhD, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa (e-mail: carolinet@nicd.ac.za).

© 2008 Lippincott Williams & Wilkins, Inc.