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

J Acquir Immune Defic Syndr. 2019 Dec 15;82(5):503-513. doi: 10.1097/QAI.0000000000002185.


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-1cART individuals by qRT-PCR.

Results: All IL-32 isoforms were significantly upregulated in HIV-1cART compared to HIV 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • Case-Control Studies
  • Drug Therapy, Combination
  • HIV Infections / blood*
  • HIV Infections / drug therapy
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukins / blood*
  • Interleukins / genetics
  • Interleukins / pharmacology
  • Leukocytes, Mononuclear
  • Protein Isoforms / blood
  • Protein Isoforms / genetics
  • Protein Isoforms / pharmacology
  • Recombinant Proteins / pharmacology
  • Transcription, Genetic / drug effects
  • Up-Regulation
  • Viral Load


  • Anti-HIV Agents
  • IL32 protein, human
  • Interleukins
  • Protein Isoforms
  • Recombinant Proteins