Host CCL3L1 gene copy number in relation to HIV-1-specific CD4+ and CD8+ T-cell responses and viral load in South African women.
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-gamma 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.
Shalekoff
Sharon
S
AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
Meddows-Taylor
Stephen
S
Schramm
Diana B
DB
Donninger
Samantha L
SL
Gray
Glenda E
GE
Sherman
Gayle G
GG
Coovadia
Ashraf H
AH
Kuhn
Louise
L
Tiemessen
Caroline T
CT
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054405:Chemokine CCL3 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D013019:South Africa; D019562:Viral Load
D054405:Chemokine CCL3