Role of interleukin 32 in human immunodeficiency virus reactivation and its link to human immunodeficiency virus-herpes simplex virus coinfection

Pedro M.M. Mesquita, Paula Preston-Hurlburt, Marla J. Keller, Nalini Vudattu, Lilia Espinoza, Michelle Altrich, Kathryn Anastos, Kevan C. Herold, Betsy C. Herold

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)614-622
Number of pages9
JournalJournal of Infectious Diseases
Volume215
Issue number4
StatePublished - Feb 15 2017

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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