Viral reservoir characteristics in lymphoid tissues of HIV-1 elite controllers
Elite controllers (ECs) maintain undetectable levels of plasma viremia in the absence of treatment, but small reservoirs of replication-competent proviruses persist in the vast majority of these persons. We longitudinally studied paired blood and inguinal lymph node samples (LNMC) from 2 ECs to better characterize distinguishing features of viral reservoir cell dynamics in ECs. In both participants, we observed a 7- to 10-fold lower frequency of intact proviruses in LNMC samples relative to reservoir cells circulating in blood. The landscape of intact proviruses in both tissue compartments was dominated by shared large clones that were frequently integrated in noncoding DNA regions, but the frequency and diversity of intact proviruses was more limited in LNMCs. Of note, over 9-10 years of longitudinal follow-up, a 3- to 18-fold reduction of intact proviruses was observed. Together, these data support the hypothesis that viral reservoirs in EC blood and lymphoid tissues are under strong, likely immune-mediated selection pressure.
Authors
- Stefano Marzi (ORCID: https://orcid.org/0000-0003-0399-4613)
- Matthias L. Cavassini (ORCID: https://orcid.org/0000-0003-0933-7833)
- Mathias Lichterfeld (ORCID: https://orcid.org/0000-0001-9865-8350)
- Ce Gao (ORCID: https://orcid.org/0000-0002-3775-790X)
- Carmen Gasca‐Capote (ORCID: https://orcid.org/0000-0002-7211-8599)
- Isabelle Roseto (ORCID: https://orcid.org/0009-0008-2976-0720)
- Fa‐Xing Yu (ORCID: https://orcid.org/0000-0003-4834-9335)
- Andrea Mastrángelo (ORCID: https://orcid.org/0000-0003-2844-6883)
- Leah Carrere (ORCID: https://orcid.org/0009-0000-2481-5501)
- Matthieu Perreau
- Chloé M. Naasz
Institutions
- Brigham and Women's Hospital (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Ragon Institute of MGH, MIT and Harvard (US)
- Office of Infectious Diseases (US)
- Instituto de Biomedicina de Sevilla (ES)
- National Research Council (LK)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1172/jci.insight.197308
- Citations
- 3
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.11
Funders
- National Science Foundation
- Bill and Melinda Gates Foundation
- amfAR, The Foundation for AIDS Research
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health