The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

Identifier: imarina:9366271

Handle: https://hdl.handle.net/20.500.11797/imarina9366271

Authors:
Gasca-Capote CLian XGao CRoseto ICJiménez-León MRGladkov GCamacho-Sojo MIPérez-Gómez AGallego ILopez-Cortes LEBachiller SVitalle JRafii-El-Idrissi Benhnia MOstos FJCollado-Romacho ARSantos JPalacios RGomez-Ayerbe CMuñoz-Medina LRuiz-Sancho AFrias MRivero-Juarez ARoca-Oporto CHidalgo-Tenorio CRull AOlalla JLopez-Ruz MAVidal FViladés CMastrangelo ACavassini MEspinosa NPerreau MPeraire JRivero ALópez-Cortes LFLichterfeld MYu XGRuiz-Mateos E

Abstract:
BACKGROUND. Persistent 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. METHODS. The 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). RESULTS. PCs 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. CONCLUSIONS. These 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. FUNDING. Instituto 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 G