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Identification of Interleukin-27 (IL-27)/IL- 27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control
Ruiz-Riol, M.; Berdnik, D.; Llano, A.; Mothe, Beatriz; Gálvez Montón, Carolina; Pérez Alvarez, Susana; Oriol Tordera, B.; Olvera Van der Stoep, Alex; Silva Arrieta, S.; Meulbroek, M.; Pujol, F.; Coll, J.; Martínez Picado, Javier; Ganoza, Carmela; Sánchez, J.; Gómez Melis, Guadalupe; Coray, Wyss; Brander, Christian
Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa; Universitat Politècnica de Catalunya. GRBIO - Grup de Recerca en Bioestadística i Bioinformàtica
Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia (P < 0.0001) and are positively correlated with proviral HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/ß-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor (IL27RA) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC.
Peer Reviewed
Àrees temàtiques de la UPC::Matemàtiques i estadística::Investigació operativa
communicome HIV HIV replication control IL-27 cytokine Th17 signaling Wnt signaling soluble communication factors
Classificació AMS::92 Biology and other natural sciences::92C Physiological, cellular and medical topics
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/publishedVersion
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