Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection

• Published in: The Journal of experimental medicine Vol. 221; no. 11
• Main Authors: Sun, Weiwei, Gao, Ce, Gladkov, Gregory Takashi, Roseto, Isabelle, Carrere, Leah, Parsons, Elizabeth M., Gasca-Capote, Carmen, Frater, John, Fidler, Sarah, Yu, Xu G., Lichterfeld, Mathias, Sandström, Eric, Darbyshire, Janet, Post, Frank, Conlon, Christopher, Anderson, Jane, Maini, Mala, Peto, Timothy, Sasieni, Peter, Miller, Veronica, Weller, Ian, Babiker, Abdel, Stöhr, Wolfgang, Pett, Sarah, Dorrell, Lucy, Pace, Matthew, Olejniczak, Natalia, Brown, Helen, Robinson, Nicola, Kopycinski, Jakub, Yang, Hongbing, Hanke, Tomáš, Crook, Alison, Kaye, Stephen, McClure, Myra, Erlwein, Otto, Lovell, Andrew, Khan, Maryam, Gabriel, Michelle, Bennett, Rachel, Sy, Aminata, Gregory, Andrew, Hudson, Fleur, Russell, Charlotte, Wood, Gemma, Box, Hanna, Kingsley, Cherry, Topping, Katie, Lever, Andrew, Wills, Mark, Fun, Alex, Bandara, Mikaila, Kelly, Damian, Collins, Simon, Markham, Alex, Rauchenberger, Mary, Sowunmi, Yinka, Shidfar, Shaadi, Hague, Dominic, Nelson, Mark, Cerrone, Maddalena, Castrillo Martinez, Nadia, Barber, Tristan, Schoolmeesters, Alexandra, Weaver, Christine, Thunder, Orla, Rowlands, Jane, Higgs, Christopher, Fedele, Serge, Bracchi, Margherita, Thomas, Lervina, Bourke, Peter, Nwokolo, Nneka, Lawrenson, Gaynor, Fiorino, Marzia, Lukha, Hinal, Kinloch, Sabine, Johnson, Margaret, Nightingale, Alice, Ngwu, Nnenna, Byrne, Patrick, Cuthbertson, Zoe, Jones, Martin, Fernandez, Tina, Clarke, Aamanda, Fisher, M., Gleig, Rebecca, Trevitt, Vittorio, Fitzpatrick, Colin, Adams, Tanya, Finnerty, Fiounnouala, Thornhill, John, Lewis, Heather, Kuldanek, Kristin, Fox, Julie, Lwanga, Julianne, Uzu, Hiromi, Lee, Ming
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 04.11.2024
• Subjects: AIDS Vaccines - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Humans; Immunity, Innate - drug effects; Male; Proviruses - genetics; Randomized Controlled Trials as Topic; Virology
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20241091

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses. Single-cell proteogenomic profiling demonstrated that cells harboring intact HIV-1 displayed a discrete phenotypic signature of immune selection by innate immune responses, characterized by a slight but significant upregulation of HLA-C, HLA-G, the IL-10 receptor, and other markers involved in innate immune regulation. Together, these results suggest an accelerated immune selection of viral reservoir cells during early-treated HIV-1 infection that seems at least partially driven by innate immune responses.