HIV-1 latency reversal and immune enhancing activity of IL-15 is not influenced by sex hormones

Authors

Carissa S. Holmberg, Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington DC, United States of America.
Callie Levinger, Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington DC, United States of America.
Marie Abongwa, Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington DC, United States of America.
Cristina Ceriani, UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America.
Nancie Archin, UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America.
Marc Siegel, The George Washington School of Medicine and Health Sciences, Washington DC, United States of America.
Mimi Ghosh, Epidemiology, The George Washington University, Washington DC, United States of America.
Alberto Bosque, Microbiology, Immunology, and Tropical Medicine, The George Washington University, Washington DC, United States of America.

Document Type

Journal Article

Publication Date

7-30-2024

Journal

JCI insight

DOI

10.1172/jci.insight.180609

Keywords

AIDS/HIV; Cytokines; Immunology; Sex hormones

Abstract

The role of different biological variables including biological sex, age, and sex hormones in HIV cure approaches is not well understood. The γc-cytokine IL-15 is a clinically relevant cytokine that promotes immune activation and mediates HIV reactivation from latency. In this work, we examine the interplay that biological sex, age, and sex hormones 17β-estradiol, progesterone, and testosterone may have on the biological activity of IL-15. We found that IL-15-mediated CD4 T cell activation was higher in female donors compared to male donors. This difference was abrogated at high 17β-estradiol concentration. Additionally, there was a positive correlation between age and both IL-15-mediated CD8 T cell activation and IFN-γ production. In a primary cell model of latency, biological sex, age, or sex hormones did not influence the ability of IL-15 to reactivate latent HIV. Finally, 17β-estradiol did not consistently affect reactivation of translation-competent reservoirs in CD4 T cells from ART-suppressed people living with HIV. Our study has found that biological sex and age, but not sex hormones, may influence some of the biological activities of IL-15. Understanding how different biological variables affect the biological activity of cure therapies will help us evaluate current and future clinical trials aimed towards HIV cure in diverse populations.

APA Citation

Holmberg, Carissa S.; Levinger, Callie; Abongwa, Marie; Ceriani, Cristina; Archin, Nancie; Siegel, Marc; Ghosh, Mimi; and Bosque, Alberto, "HIV-1 latency reversal and immune enhancing activity of IL-15 is not influenced by sex hormones" (2024). GW Authored Works. Paper 5217.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5217

Department

Microbiology, Immunology, and Tropical Medicine