HSV-2 exacerbates HIV by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T cell populations and HIV reservoirs.


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


The phenotype of CD4, but not CD8, T cells differed in HIV+/HSV-2+ versus HIV+/HSV-2- (overall p=0.002) 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 CA-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 addition of a RUNX1 inhibitor.


HSV-2 is associated with phenotypic changes in CD4+ T cells including a decrease in IL-32, which may contribute to increased HIV reservoirs. IL-32 blockade may facilitate HIV reactivation to improve “shock and kill” strategies.

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