TY - JOUR
T1 - Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals
T2 - Potential Role in Persistent Inflammation and Transcription from Stable HIV-1 Reservoirs
AU - Zaidan, Sarah M.
AU - Leyre, Louise
AU - Bunet, Rémi
AU - Larouche-Anctil, Etienne
AU - Turcotte, Isabelle
AU - Sylla, Mohamed
AU - Chamberland, Annie
AU - Chartrand-Lefebvre, Carl
AU - Ancuta, Petronela
AU - Routy, Jean Pierre
AU - Baril, Jean Guy
AU - Trottier, Benoit
AU - Macpherson, Paul
AU - Trottier, Sylvie
AU - Harris, Marianne
AU - Walmsley, Sharon
AU - Conway, Brian
AU - Wong, Alexander
AU - Thomas, Réjean
AU - Kaplan, Robert C.
AU - Landay, Alan L.
AU - Durand, Madeleine
AU - Chomont, Nicolas
AU - Tremblay, Cécile L.
AU - El-Far, Mohamed
N1 - Publisher Copyright:
© 2019 The Author(s). Published by Wolters Kluwer Health, Inc.
PY - 2019/12/15
Y1 - 2019/12/15
N2 - Background:Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4+ T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory.Setting and Methods:Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4+ T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4+ T-cells from HIV-1+cART+ individuals by qRT-PCR.Results:All IL-32 isoforms were significantly upregulated in HIV-1+cART+ compared to HIVneg individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4+ T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4+ T-cells isolated from combined antiretroviral therapy-treated individuals.Conclusions:Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.
AB - Background:Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest that IL-32 may enhance HIV-1 replication by activating the HIV-1 primary targets, CD4+ T-cells. Indeed, IL-32 is expressed in multiple isoforms, some of which are proinflammatory, whereas others are anti-inflammatory.Setting and Methods:Here, we aimed to determine the relative expression of IL-32 isoforms and to test their inflammatory nature and potential to induce HIV-1 production in latently infected cells from virologically suppressed HIV-infected individuals. IL-32 and other cytokines were quantified from plasma and supernatant of CD4+ T-cells by ELISA. Transcripts of IL-32 isoforms were quantified by qRT-PCR in peripheral blood mononuclear cells. The impact of recombinant human IL-32 isoforms on HIV-1 transcription was assessed in CD4+ T-cells from HIV-1+cART+ individuals by qRT-PCR.Results:All IL-32 isoforms were significantly upregulated in HIV-1+cART+ compared to HIVneg individuals with IL-32β representing the dominantly expressed isoform, mainly in T-cells and NK-cells. At the functional level, although IL-32γ induced typical proinflammatory cytokines (IL-6 and IFN-γ) in TCR-activated CD4+ T-cells, IL-32α showed an anti-inflammatory profile by inducing IL-10 but not IL-6 or IFN-γ. However, IL-32β showed a dual phenotype by inducing both pro- and anti-inflammatory cytokines. Interestingly, consistent with its highly pro-inflammatory nature, IL-32γ, but not IL-32α or IL-32β, induced HIV-1 production in latently infected CD4+ T-cells isolated from combined antiretroviral therapy-treated individuals.Conclusions:Our data report on the differential expression of IL-32 isoforms and highlight the potential role of IL-32, particularly the γ isoform, in fueling persistent inflammation and transcription of viral reservoir in HIV-1 infection.
KW - HIV-1
KW - HIV-1 reservoir
KW - IL-32
KW - inflammation
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U2 - 10.1097/QAI.0000000000002185
DO - 10.1097/QAI.0000000000002185
M3 - Article
C2 - 31714430
AN - SCOPUS:85074866385
SN - 1525-4135
VL - 82
SP - 503
EP - 513
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 5
ER -
