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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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

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