Protection versus pathology in aviremic and high viral load HIV-2 infection - The pivotal role of immune activation and T-cell kinetics

Andrea Hegedus, Samuel Nyamweya, Yan Zhang, Sheila Govind, Richard Aspinall, Alla Mashanova, Vincent A.A. Jansen, Hilton Whittle, Assan Jaye, Katie L. Flanagan, Derek C. Macallan

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Abstract

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.

Original languageEnglish
Pages (from-to)752-761
Number of pages10
JournalJournal of Infectious Diseases
Volume210
Issue number5
DOIs
Publication statusPublished - 1 Sep 2014
Externally publishedYes

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HIV-2
Virus Diseases
Viral Load
Pathology
T-Lymphocytes
HIV-1
T-Cell Antigen Receptor
Gambia
Western Africa
Deuterium
HLA-DR Antigens
Flow Cytometry
Acquired Immunodeficiency Syndrome
HIV
Phenotype
Glucose
Infection

Bibliographical note

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • CD4
  • CD8
  • HIV pathogenesis
  • HIV-1
  • HIV-2
  • Immune activation
  • Immune memory
  • T-cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Protection versus pathology in aviremic and high viral load HIV-2 infection - The pivotal role of immune activation and T-cell kinetics. / Hegedus, Andrea; Nyamweya, Samuel; Zhang, Yan; Govind, Sheila; Aspinall, Richard; Mashanova, Alla; Jansen, Vincent A.A.; Whittle, Hilton; Jaye, Assan; Flanagan, Katie L.; Macallan, Derek C.

In: Journal of Infectious Diseases, Vol. 210, No. 5, 01.09.2014, p. 752-761.

Research output: Contribution to journalArticle

Hegedus, A, Nyamweya, S, Zhang, Y, Govind, S, Aspinall, R, Mashanova, A, Jansen, VAA, Whittle, H, Jaye, A, Flanagan, KL & Macallan, DC 2014, 'Protection versus pathology in aviremic and high viral load HIV-2 infection - The pivotal role of immune activation and T-cell kinetics' Journal of Infectious Diseases, vol. 210, no. 5, pp. 752-761. https://doi.org/10.1093/infdis/jiu165
Hegedus, Andrea ; Nyamweya, Samuel ; Zhang, Yan ; Govind, Sheila ; Aspinall, Richard ; Mashanova, Alla ; Jansen, Vincent A.A. ; Whittle, Hilton ; Jaye, Assan ; Flanagan, Katie L. ; Macallan, Derek C. / Protection versus pathology in aviremic and high viral load HIV-2 infection - The pivotal role of immune activation and T-cell kinetics. In: Journal of Infectious Diseases. 2014 ; Vol. 210, No. 5. pp. 752-761.
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T1 - Protection versus pathology in aviremic and high viral load HIV-2 infection - 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.

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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.

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KW - Immune memory

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