title: Role of Interleukin 32 in Human Immunodeficiency Virus Reactivation and Its Link to Human Immunodeficiency Virus-Herpes Simplex Virus Coinfection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Pedro M M
authors.initials: PMM
authors.lastname: Mesquita
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Preston-Hurlburt
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Keller
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Nalini
authors.initials: N
authors.lastname: Vudattu
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Lilia
authors.initials: L
authors.lastname: Espinoza
authors.affiliation: Viracor-IBT Laboratories, Lee's Summit, Missouri, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Altrich
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.|Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D060085:Coinfection / Q000821:virology; D050676:Core Binding Factor Alpha 2 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D012367:RNA, Viral / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004279:DNA, Viral; C496971:IL32 protein, human; D007378:Interleukins; D012367:RNA, Viral; C493728:RUNX1 protein, human; D011994:Recombinant Proteins
keywords: CD4+; HIV reservoirs; Herpes simplex virus; IL-32; human immunodeficiency virus; T cells