Upregulation of IL-32 Isoforms in Virologically Suppressed HIV-Infected Individuals: Potential Role in Persistent Inflammation and Transcription from Stable HIV-1 Reservoirs

Sarah M. Zaidan, Louise Leyre, Rémi Bunet, Etienne Larouche-Anctil, Isabelle Turcotte, Mohamed Sylla, Annie Chamberland, Carl Chartrand-Lefebvre, Petronela Ancuta, Jean Pierre Routy, Jean Guy Baril, Benoit Trottier, Paul Macpherson, Sylvie Trottier, Marianne Harris, Sharon Walmsley, Brian Conway, Alexander Wong, Réjean Thomas, Robert C. KaplanAlan L. Landay, Madeleine Durand, Nicolas Chomont, Cécile L. Tremblay, Mohamed El-Far

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)503-513
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number5
StatePublished - Dec 15 2019
Externally publishedYes


  • HIV-1
  • HIV-1 reservoir
  • IL-32
  • inflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)


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