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

• Published in: Cell host & microbe Vol. 31; no. 10; pp. 1714 - 1731.e9
• Main Authors: Banga, Riddhima, Procopio, Francesco Andrea, Lana, Erica, Gladkov, Gregory T., Roseto, Isabelle, Parsons, Elizabeth M., Lian, Xiaodong, Armani-Tourret, Marie, Bellefroid, Maxime, Gao, Ce, Kauzlaric, Annamaria, Foglierini, Mathilde, Alfageme-Abello, Oscar, Sluka, Susanna H.M., Munoz, Olivia, Mastrangelo, Andrea, Fenwick, Craig, Muller, Yannick, Mkindi, Catherine Gerald, Daubenberger, Claudia, Cavassini, Matthias, Trunfio, Rafael, Déglise, Sébastien, Corpataux, Jean-Marc, Delorenzi, Mauro, Lichterfeld, Mathias, Pantaleo, Giuseppe, Perreau, Matthieu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.10.2023
• Subjects: Animals; Anti-Retroviral Agents - therapeutic use; CD4-Positive T-Lymphocytes; Dendritic Cells; HIV; HIV cure; HIV Infections; HIV persistence; HIV reservoir; HIV single-genome sequencing; Humans; intact HIV; lymph node; Lymph Nodes; replication-competent virus; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; T follicular helper cells; dendritic cells; HIV; intact HIV; lymph node; HIV persistence; HIV reservoir; T follicular helper cells; HIV cure; HIV single-genome sequencing; replication-competent virus
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2023.08.020

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. [Display omitted] •LN DCs support active cycles of de novo HIV replication•LN DCs harbor intact HIV proviruses within active host transcription units•LN DCs harbor inducible replication-competent HIV despite years of suppressive ART Although DCs play a major role during HIV dissemination, their implications in immunopathogenesis and persistence has long-time been neglected. Banga et al. demonstrate that lymph node DCs containing inducible replication-competent virus can be detected after years of suppressive ART, opening new avenues for developing therapeutic interventions for HIV cure.