Format

Send to

Choose Destination
J Infect Dis. 2017 Feb 15;215(4):614-622. doi: 10.1093/infdis/jiw612.

Role of Interleukin 32 in Human Immunodeficiency Virus Reactivation and Its Link to Human Immunodeficiency Virus-Herpes Simplex Virus Coinfection.

Author information

1
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
3
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
4
Viracor-IBT Laboratories, Lee's Summit, Missouri, USA.
5
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
6
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.

Abstract

Background:

Herpes simplex virus type 2 (HSV-2; herpes) exacerbates human immunodeficiency virus type 1 (HIV) by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T-cells and HIV reservoirs.

Methods:

Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative and HIV-uninfected controls were analyzed by flow cytometry. Cell-associated HIV DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant interleukin 32γ (IL-32γ), and a RUNX1 inhibitor. RNA was assessed by nanostring.

Results:

CD4, but not CD8, T-cell phenotypes differed in HIV+/HSV-2+ versus HIV+/HSV-2- (overall P = .002) with increased frequency of CCR5+, CXCR4+, PD-1+, and CD69+ and decreased frequency of CCR10+ and CCR6+ T-cells. The changes were associated with higher HIV DNA. Paradoxically, IL-32, a proinflammatory cytokine, was lower in subpopulations of CD4+ T-cells in HSV-2+ versus HSV-2- women. Recombinant IL-32γ blocked HIV reactivation in CD4+ T-cells and was associated with an increase in RUNX1 expression; the blockade was overcome by a RUNX1 inhibitor.

Conclusions:

Herpes is associated with phenotypic changes in CD4+ T-cells, including a decrease in IL-32, which may contribute to increased HIV reservoirs. Blocking IL-32 may facilitate HIV reactivation to improve shock and kill strategies.

KEYWORDS:

CD4+; HIV reservoirs; Herpes simplex virus; IL-32; human immunodeficiency virus; T cells

PMID:
28007920
PMCID:
PMC5388286
DOI:
10.1093/infdis/jiw612
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center