The authors have previously found that memory CD4+ T cells can be detected in the peripheral blood and lymph nodes of both HIV-1-infected and uninfected participants that express low levels of SAMHD1 (SAMHD1low). These cells are enriched in Th17 and Tfh subsets, which are two populations that are preferentially targeted by HIV. The authors were interested in whether SAMHD1low CD4+ T cells harbour replication-competent virus and compartimentalised HIV genomes. They sorted memory CD4+CD45RO+SAMHD1low, CD4+CD45RO+SAMHD1+ and naive CD4+CD45RO-SAMHD1+ cells from HIV-infected patients being treated with antiretroviral therapy (ART) and quantified the HIV DNA present together with sequencing of partial env (C2/V3) sequences and phenotypic characterisation of the cells. They found that SAMHD1low cells include novel Th17 CCR6+ subsets that lack CXCR3 and CCR4 (CCR6+DN). There is a significant decrease in the percentage of Th17 in the SAMHD1low compartment in infected compared with uninfected patients (41% vs. 55%), while the percentage of CCR6+DN significantly increases (7.95% vs. 3.8%). In addition, memory SAMHD1low cells in HIV-infected patients harbour significantly higher levels of HIV DNA compared with memory SAMHD1+ cells (4.5 vs. 3.8 log/106 cells), while naïve SAMHD1+ had significantly lower levels (3.1 log/106 cells). The authors found that SAMHD1low cells also contain p24-producing cells and phylogenetics identified well-segregated HIV DNA populations with compartmentalisation between SAMHD1low and SAMHD1+ memory cells, together with limited viral exchange. The percentage of Ki67+ cells was significantly higher in SAMHD1low compared with SAMHD1+ cells, and there was a positive association between the levels of HIV DNA and Ki67+ in memory SAMHD1low cells but not in memory and naïve SAMHD1+ CD4+ T cells. Therefore these results suggest that proliferative memory SAMHD1low cells contribute to viral persistence.
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