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

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


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.

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Coinfection / virology
  • Core Binding Factor Alpha 2 Subunit / antagonists & inhibitors
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Cross-Sectional Studies
  • DNA, Viral / isolation & purification
  • Female
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Herpes Genitalis / immunology*
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Interleukins / antagonists & inhibitors
  • Interleukins / immunology*
  • Leukocytes, Mononuclear / immunology
  • Middle Aged
  • RNA, Viral / isolation & purification
  • Recombinant Proteins / metabolism
  • Viral Load
  • Young Adult


  • Core Binding Factor Alpha 2 Subunit
  • DNA, Viral
  • IL32 protein, human
  • Interleukins
  • RNA, Viral
  • RUNX1 protein, human
  • Recombinant Proteins