Advertisement

ResearchIn-Press PreviewAIDS/HIVCell biologyInfectious disease Open Access | 10.1172/jci.insight.198415

Impact of specific ligands and HIV latency reversal agents on estrogen Receptor alpha in CD4+ T cells

Cristina Ceriani,1 Priya Khetan,1 Anthony Abeyta-Lopez,1 Kena J. Lemu,1 Prachi Meher,1 Brigitte Allard,1 Katherine S. James,1 Anne-Marie W. Turner,1 David M. Margolis,1 and Nancie M. Archin1

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Ceriani, C. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Khetan, P. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Abeyta-Lopez, A. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Lemu, K. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Meher, P. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Allard, B. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by James, K. in: PubMed | Google Scholar

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Turner, A. in: PubMed | Google Scholar |

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Margolis, D. in: PubMed | Google Scholar |

1UNC HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

Find articles by Archin, N. in: PubMed | Google Scholar

Published July 10, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.198415.
Copyright © 2026, Ceriani et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 10, 2026 - Version history
View PDF
Abstract

The estrogen receptor is hypothesized to directly influence HIV-transcription and latency but is also critical for immune signaling. However, the mechanisms of action of the estrogen receptor (ER) in immune cells in the context of HIV are limited, and relevant to HIV cure strategies, the influence of latency reversal agents (LRAs) on the ER pathway are unknown. We evaluated a) the impact of estrogen (E2) on the nuclear translocation of estrogen receptor α (ERα) in CD4+ T cells, b) the ability of Fulvestrant, a selective estrogen receptor degrader (SERD), and ARV-471, a novel, potent, PROteolysis TArgeting Chimera (PROTAC) selective ERα degrader to modulate ER and c) the impact of different classes of LRAs on ER signaling. In contrast to what has been demonstrated in oncology, E2 does not induce ERα nuclear translocation in CD4+ T cells. Similarly, neither Fulvestrant nor ARV-471 induced degradation of ERα in CD4+ T cells. LRAs significantly downregulated ERα gene and protein expression in both PBMCs and CD4+ T cells. Collectively, our results suggest that estrogen influences on HIV transcription are not likely a consequence of canonical nuclear ERα mechanisms. The consequences of LRA downregulation of ER, a protein important for immune signaling, warrants further investigation.

Supplemental material

View Unedited blot and gel images

View Supplemental figures

Version history
  • Version 1 (July 10, 2026): In-Press Preview
Advertisement
Advertisement