Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART
Riddhima Banga, Francesco A. 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 Muñoz, Andrea Mastrángelo, Craig Fenwick, Yannick D. Müller, Catherine Mkindi, Claudia Daubenberger, Matthias Cavassini, Rafael Trunfio, Sébastien Déglise, Jean-Marc Corpataux, Mauro Delorenzi, Mathias Lichterfeld, Giuseppe Pantaleo, Matthieu Perreau
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.