Protection Versus Pathology in Aviremic and High Viral Load HIV-2 Infection—The Pivotal Role of Immune Activation and T-cell Kinetics

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.

Preservation of Lymphopoietic Potential and Virus Suppressive Capacity by CD8+ T Cells in HIV-2–Infected Controllers

“…We and others previously reported that thymic function is preserved in HIV-2-infected individuals with low viral load (25). It was also recently shown that HIV-2 infection in thymocytes is impaired (26,27), which may contribute to the maintenance of high CD4 + T cell counts in HIV-2-infected patients. In this study, we measured sjTREC levels in total PBMC to estimate thymic function in HIC2.…”

SAMHD1: At the Crossroads of Cell Proliferation, Immune Responses, and Virus Restriction

“…However, HIV-2 infection represents a natural model of retroviral disease in which nonprogression and lower levels of immune activation appear to be the norm [73]. Importantly, viral replication and high viremia are not sufficient to explain the immunopathogenesis of all retroviruses because high-level viremia without immune cell activation may be tolerated without disease, as in the case of sooty mangabey SIV infection [73,74].…”

“…However, HIV-2 infection represents a natural model of retroviral disease in which nonprogression and lower levels of immune activation appear to be the norm [73]. Importantly, viral replication and high viremia are not sufficient to explain the immunopathogenesis of all retroviruses because high-level viremia without immune cell activation may be tolerated without disease, as in the case of sooty mangabey SIV infection [73,74]. These differences have led to the hypothesis that the immune system is able to differentially recognize and trigger an innate immune response through sensing of viral elements (for a recent review, see [75]), leading to aberrant cell activation and immunopathogenesis.…”

Quantification of naive and memory T-cell turnover during HIV-1 infection

“…The introduction of stable isotope labeling into the field of immunology has paved the way for reliable quantification of T-cell dynamics. Previous studies based on 2 Hglucose or 2 H 2 O labeling demonstrated the great potential of this technique for studying lymphocyte turnover [7,9,11,12,16,[18][19][20][21][22][23][24].…”