Proliferative memory SAMHD1(low) CD4(+) T cells harbour high levels of HIV-1 with compartmentalized viral populations

We previously reported the presence of memory CD4(+) T cells that express low levels of SAMHD1 (SAMHD1(low)) in peripheral blood and lymph nodes from both HIV-1 infected and uninfected individuals. These cells are enriched in Th17 and Tfh subsets, two populations known to be preferentially targeted by HIV-1. Here we investigated whether SAMHD1(low) CD4(+) T-cells harbour replication-competent virus and compartimentalized HIV-1 genomes. We sorted memory CD4(+)CD45RO(+)SAMHD1(low), CD4(+)CD45RO(+)SAMHD1(+) and naive CD4(+)CD45RO(-)SAMHD1(+) cells from HIV-1-infected patients on anti-retroviral therapy (c-ART) and performed HIV-1 DNA quantification, ultra-deep-sequencing of partial env (C2/V3) sequences and phenotypic characterization of the cells. We show that SAMHD1(low) cells include novel Th17 CCR6(+) subsets that lack CXCR3 and CCR4 (CCR6(+)DN). There is a decrease of the % of Th17 in SAMHD1(low) compartment in infected compared to uninfected individuals (41% vs 55%, p<0.05), whereas the % of CCR6(+)DN increases (7.95% vs 3.8%, p<0.05). Moreover, in HIV-1 infected patients, memory SAMHD1(low) cells harbour high levels of HIV-1 DNA compared to memory SAMHD1(+) cells (4.5 vs 3.8 log/10(6)cells, respectively, p<0.001), while naïve SAMHD1(+) showed significantly lower levels (3.1 log/10(6)cells, p<0.0001). Importantly, we show that SAMHD1(low) cells contain p24-producing cells. Moreover, phylogenetic analyses revealed well-segregated HIV-1 DNA populations with compartmentalization between SAMHD1(low) and SAMHD1(+) memory cells, and limited viral exchange. As expected, the % of Ki67(+) cells was significantly higher in SAMHD1(low) compared to SAMHD1(+) cells. There was positive association between levels of HIV-1 DNA and Ki67(+) in memory SAMHD1(low) cells, but not in memory and naïve SAMHD1(+) CD4(+) T-cells. Altogether, these data suggest that proliferative memory SAMHD1(low) cells contribute to viral persistence.