TY - JOUR
T1 - Protection Versus Pathology in Aviremic and High Viral Load HIV-2 Infection
T2 - The Pivotal Role of Immune Activation and T-cell Kinetics
AU - Hegedus, Andrea
AU - Nyamweya, Samuel
AU - Zhang, Yan
AU - Govind, Sheila
AU - Aspinall, Richard
AU - Mashanova, Alla
AU - Jansen, Vincent A. A.
AU - Whittle, Hilton
AU - Jaye, Assan
AU - Flanagan, Katie L
AU - Macallan, Derek C.
N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
PY - 2014/9/1
Y1 - 2014/9/1
N2 - BACKGROUND: Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status.
METHODS: We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance.
RESULTS: Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls <HIV-2-LV <HIV-1 <HIV-2-HV (P < .01 for all cell types). A similar trend was observed in the pattern of in vivo turnover of memory CD4(+) and CD8(+) T-cells and TREC depletion in naive CD4(+) T-cells, although naive T-cell turnover was relatively unaffected by either infection. T-cell turnover, immune activation, and progressor status were closely associated.
CONCLUSIONS: HIV-2 non-progressors have low rates of T-cell turnover (both CD4(+) and CD8(+)) and minimal immune activation; high viral load HIV-2 progressors had high values, similar to or exceeding those in HIV-1 infection.
AB - BACKGROUND: Many human immunodeficiency virus (HIV)-2-infected individuals remain aviremic and behave as long-term non-progressors but some progress to AIDS. We hypothesized that immune activation and T-cell turnover would be critical determinants of non-progressor/progressor status.
METHODS: We studied 37 subjects in The Gambia, West Africa: 10 HIV-negative controls, 10 HIV-2-infected subjects with low viral loads (HIV-2-LV), 7 HIV-2-infected subjects with high viral loads (HIV-2-HV), and 10 with HIV-1 infection. We measured in vivo T-cell turnover using deuterium-glucose labeling, and correlated results with T-cell phenotype (by flow cytometry) and T-cell receptor excision circle (TREC) abundance.
RESULTS: Immune activation (HLA-DR/CD38 coexpression) differed between groups with a significant trend: controls <HIV-2-LV <HIV-1 <HIV-2-HV (P < .01 for all cell types). A similar trend was observed in the pattern of in vivo turnover of memory CD4(+) and CD8(+) T-cells and TREC depletion in naive CD4(+) T-cells, although naive T-cell turnover was relatively unaffected by either infection. T-cell turnover, immune activation, and progressor status were closely associated.
CONCLUSIONS: HIV-2 non-progressors have low rates of T-cell turnover (both CD4(+) and CD8(+)) and minimal immune activation; high viral load HIV-2 progressors had high values, similar to or exceeding those in HIV-1 infection.
U2 - 10.1093/infdis/jiu165
DO - 10.1093/infdis/jiu165
M3 - Article
C2 - 24803534
SN - 1537-6613
VL - 210
SP - 752
EP - 761
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -