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

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

Author information

1
Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
2
Départment de microbiologie, infectiologie et immunologie, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
3
McGill University Health Centre Research Institute, Montréal, QC, Canada.
4
Centre de médecine urbaine du Quartier latin, Montréal, QC, Canada.
5
Ottawa General Research Institute, Ottawa, ON, Canada.
6
Centre Hospitalier de l'Université Laval, Quebec, QC, Canada.
7
AIDS Research Program, St. Paul's Hospital, Vancouver, BC, Canada.
8
Division of Infectious Diseases, University Health Network, Toronto, ON, Canada.
9
Infectious Diseases Clinic, Regina Qu'Appelle Health Region, Regina, SK, Canada.
10
Clinique Médicale l'Actuel, Montréal, QC, Canada.
11
Albert Einstein College of Medicine, Bronx, NY.
12
Rush University Medical Center, Chicago, IL.

Abstract

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.

PMID:
31714430
PMCID:
PMC6857723
[Available on 2020-12-15]
DOI:
10.1097/QAI.0000000000002185

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