Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART

Riddhima Banga; Francesco Andrea Procopio; Erica Lana; Gregory T Gladkov; Isabelle Roseto; Elizabeth M Parsons; Xiaodong Lian; Marie Armani-Tourret; Maxime Bellefroid; Ce Gao; Annamaria Kauzlaric; Mathilde Foglierini; Oscar Alfageme-Abello; Susanna H M Sluka; Olivia Munoz; Andrea Mastrangelo; Craig Fenwick; Yannick Muller; Catherine Gerald Mkindi; Claudia Daubenberger; Matthias Cavassini; Rafael Trunfio; Sébastien Déglise; Jean-Marc Corpataux; Mauro Delorenzi; Mathias Lichterfeld; Giuseppe Pantaleo; Matthieu Perreau

doi:10.1016/j.chom.2023.08.020

Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART

Cell Host Microbe. 2023 Oct 11;31(10):1714-1731.e9. doi: 10.1016/j.chom.2023.08.020. Epub 2023 Sep 25.

Authors

Riddhima Banga¹, Francesco Andrea Procopio¹, Erica Lana¹, Gregory T Gladkov², Isabelle Roseto², Elizabeth M Parsons³, Xiaodong Lian³, Marie Armani-Tourret², Maxime Bellefroid², Ce Gao², Annamaria Kauzlaric⁴, Mathilde Foglierini¹, Oscar Alfageme-Abello¹, Susanna H M Sluka⁵, Olivia Munoz¹, Andrea Mastrangelo¹, Craig Fenwick¹, Yannick Muller¹, Catherine Gerald Mkindi⁶, Claudia Daubenberger⁷, Matthias Cavassini⁸, Rafael Trunfio⁹, Sébastien Déglise⁹, Jean-Marc Corpataux⁹, Mauro Delorenzi⁴, Mathias Lichterfeld³, Giuseppe Pantaleo¹⁰, Matthieu Perreau¹¹

Affiliations

¹ Services of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Translational Bioinformatics and Statistics Department of Oncology, University of Lausanne Swiss Cancer Center, Lausanne, Switzerland.
⁵ Newborn Screening Switzerland, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁶ Ifakara Health Institute, Bagamoyo, United Republic of Tanzania; Department of Medical Parasitology and Infection Biology, Clinical Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁷ Department of Medical Parasitology and Infection Biology, Clinical Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, 4001 Basel, Switzerland.
⁸ Services of Infectious Diseases, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
⁹ Services of Vascular Surgery, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
¹⁰ Services of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland; Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland.
¹¹ Services of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland. Electronic address: matthieu.perreau@chuv.ch.

PMID: 37751747
DOI: 10.1016/j.chom.2023.08.020

Abstract

Although gut and lymph node (LN) memory CD4 T cells represent major HIV and simian immunodeficiency virus (SIV) tissue reservoirs, the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due to difficulties to access lymphoid tissue samples. In this study, we show that LN migratory and resident DC subpopulations harbor distinct phenotypic and transcriptomic profiles. Interestingly, both LN DC subpopulations contain HIV intact provirus and inducible replication-competent HIV despite the expression of the antiviral restriction factor SAMHD1. Notably, LN DC subpopulations isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbor replication-competent virus that can be induced upon TLR7/8 stimulation. Taken together, these results uncover a potential important contribution of LN DCs to HIV infection in the presence of ART.

Keywords: HIV; HIV cure; HIV persistence; HIV reservoir; HIV single-genome sequencing; T follicular helper cells; dendritic cells; intact HIV; lymph node; replication-competent virus.

MeSH terms

Animals
Anti-Retroviral Agents / therapeutic use
CD4-Positive T-Lymphocytes
Dendritic Cells
HIV Infections*
Humans
Lymph Nodes
Simian Acquired Immunodeficiency Syndrome*
Simian Immunodeficiency Virus*

Substances

Anti-Retroviral Agents

Grants and funding

UM1 AI164560/AI/NIAID NIH HHS/United States