Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy
Despite antiretroviral therapy (ART), HIV-1 persists in latently infected CD4<sup>+</sup> T cells, preventing a cure. Antigens drive the proliferation of infected cells, precluding latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood because most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4<sup>+</sup> T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from people living with HIV-1 on long-term ART and assessed T cell activation and HIV-1 RNA expression upon coculture with autologous dendritic cells (DCs) presenting cognate antigens. Presentation of cognate antigens ex vivo induced broad T cell activation (median 42-fold increase in CD154<sup>+</sup>CD69<sup>+</sup> cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity and viral rebound upon ART interruption.
Authors
- Karam Mounzer (ORCID: https://orcid.org/0000-0001-8537-7103)
- Fengting Wu (ORCID: https://orcid.org/0000-0001-6320-8288)
- Janet D. Siliciano (ORCID: https://orcid.org/0000-0001-6712-3775)
- Milica Moskovljevic (ORCID: https://orcid.org/0000-0003-0436-6854)
- Rebecca Hoh (ORCID: https://orcid.org/0000-0001-5112-4220)
- Francesco R. Simonetti (ORCID: https://orcid.org/0000-0002-4165-660X)
- Jun Lai (ORCID: https://orcid.org/0009-0008-6435-2888)
- James R. White (ORCID: https://orcid.org/0000-0002-7535-9179)
- Nathan L. Board (ORCID: https://orcid.org/0000-0002-5208-9970)
- Pablo Tebas (ORCID: https://orcid.org/0000-0001-5345-7942)
- Steven G. Deeks (ORCID: https://orcid.org/0000-0001-6371-747X)
- Filippo Dragoni (ORCID: https://orcid.org/0000-0002-8148-9914)
- Luis J. Montaner (ORCID: https://orcid.org/0000-0001-5799-6759)
- Robert F. Siliciano (ORCID: https://orcid.org/0000-0002-1764-1993)
- Hao Zhang (ORCID: https://orcid.org/0000-0002-1304-5895)
- Kenneth Lynn
Institutions
- The Wistar Institute (US)
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- University of California, San Francisco (US)
- Johns Hopkins Medicine (US)
- Resphera Biosciences (US)
- University of San Francisco (US)
- University of Pennsylvania (US)
- Philadelphia Fight (US)
Publication Details
- Journal
- Immunity
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1016/j.immuni.2024.11.002
- Citations
- 9
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.64
Funders
- Howard Hughes Medical Institute
- Delaney AIDS Research Enterprise
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Johns Hopkins University
- Philadelphia Foundation
- National Institutes of Health
- Johns Hopkins University Press
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases
- National Institute of Dental and Craniofacial Research