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Caractérisation et rôle des lymphocytes T CD4+ mémoires SAMHD1low au cours de l'infection par le VIH-1

Abstract : We have previously reported the presence of memory CD4+ T cells that display low levels of SAMHD1 (SAMHD1low ) enriched in Th17 and Tfh cells. Here we investigated gene expression profile and the size and composition of HIV DNA population in SAMHD1 low cells.A total of 36 individuals on c-ART (median: 7y) with median CD4+ counts and nadir of 549 cells/ul and 210 cells/ul respectively, including 6 elite controllers (EC, CD4+: 900 cells/ul) and 8 healthy donors were studied. Blood memory CD4+ CD45RO+ SAMHD1low, CD45RO+ SAMHD1high and naive CD45RO- SAMHD1high cells were sorted. Cell associated HIV-1 DNA levels were quantified (HIV DNA Cell, Biocentric) and ultra-deep-sequencing (UDS, 454/Roche) of partial env (C2/V3) HIV-1 DNA was performed. Gene expression profile on sorted cells was deternined with RNA-Sequencing (Illumina RNASeq technology). Levels of HIV-1 DNA were significantly higher in memory SAMHD1low cells compared to SAMHD1high cells (4.5 [3.1-6.2] vs 3.8 [2.9-5.7] log/10 6 cells, respectively, p=0.02) among c-ART individuals, while naïve CD45RO- SAMHD1high showed lower levels (3.1 [1.6-4.4]). EC exhibited low HIV-1 DNA level in both SAMHD1low and SAMHD1high (1.6 and 2.3 log/10 6 cells respectively p>0.05). Naïve CD45RO - SAMHD1 high cells from EC showed lower DNA compared to naïve cells from c-ART pts (1.6 and 3.1 log/10 6 cells, respectively, p=0.01). Phylogenetic analyses revealed well-segregated HIV-DNA populations between subsets with significant compartmentalization between SAMHD1low and SAMHD1high cells in all but 2 participants (p<0.001) and limited viral exchange. Moreover SAMHD1low cells exhibited a distinct gene profile as compared to SAMHD1high allowing thus further characterisation of these cells.This pilot study revealed distinct HIV DNA populations in size and composition associated with unique genes profile in memory SAMHD1low cells. We show that memory SAMHD1low cells exhibit distinct genes profile which segregates them from the SAMHD1 high counterpart, and contain the highest level of HIV-1 DNA. We reveal distinct/well-segregated HIV-1 DNA populations in both subsets, suggesting minimal viral exchange.
Keywords : Reservoir Samhd1
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Submitted on : Friday, December 6, 2019 - 12:04:08 PM
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Lylia Hani. Caractérisation et rôle des lymphocytes T CD4+ mémoires SAMHD1low au cours de l'infection par le VIH-1. Médecine humaine et pathologie. Université Paris-Est, 2018. Français. ⟨NNT : 2018PESC0087⟩. ⟨tel-02396985⟩



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