The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.
СтатьяПоддержка службы здравоохранения СШАПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gasca-Capote Carmen, Lian Xiaodong, Gao Ce, Roseto Isabelle C, Jiménez-León María Reyes, Gladkov Gregory, Camacho-Sojo María Inés, Pérez-Gómez Alberto, Gallego Isabel, Lopez-Cortes Luis E, Bachiller Sara, Vitalle Joana, Rafii-El-Idrissi Benhnia Mohamed, Ostos Francisco J, Collado-Romacho Antonio R, Santos Jesús, Palacios Rosario, Gomez-Ayerbe Cristina, Muñoz-Medina Leopoldo, Ruiz-Sancho Andrés, Frias Mario, Rivero-Juarez Antonio, Roca-Oporto Cristina, Hidalgo-Tenorio Carmen, Rull Anna, Olalla Julian, Lopez-Ruz Miguel A, Vidal Francesc, Viladés Consuelo, Mastrangelo Andrea, Cavassini Matthias, Espinosa Nuria, Perreau Matthieu, Peraire Joaquin, Rivero Antonio, López-Cortes Luis F, Lichterfeld Mathias, Yu Xu G, Ruiz-Mateos Ezequiel
Аннотация
BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.