CD34+ monocyte subset is highly susceptible to HIV-1 infection

HIV-1 persists in cellular reservoirs despite effective antiretroviral therapy (ART). CD4+ T cells are the well-known reservoir, but there is growing evidence that myeloid cells, including circulating monocytes, are also a clinically relevant reservoir. However, it is unclear what are preferentially infected monocyte subsets in vivo. Here, we show that a monocyte fraction expressing the stem cell marker CD34 is more susceptible to HIV-1 infection than the CD34-negative major subset. In ART-untreated viremic patients, CD34+ fraction increased in the percentage in total monocytes, and harbored more proviral DNA than the major subset. Consistent with this, when compared to the major subset, CD34+ fraction expressed HIV-1 receptors (CD4 and CCR5) at higher levels and HIV-1 restriction factors (MX2 and SAMHD1) at lower levels. Interestingly, proviral DNA was detected in CD34+ fraction of ART-treated virologically suppressed patients. CD34+ monocytes were also present in lymph nodes, and expressed CD4 and CCR5 at higher levels than the major subset, as observed for peripheral blood. Moreover, CD34+ monocytes present in peripheral blood and lymph nodes highly expressed CCR7 and sphingosine-1-phosphate receptor 1 (S1PR1), critical regulators of in vivo cellular trafficking. Our findings suggest that circulating CD34+ monocytes are infected with residual HIV-1 after migrating into tissues including lymph nodes and return to circulation, which explains the detection of proviral DNA in the cells even after long-term ART. In order to identifiy the feature of monocyte subsets, CD34+ and CD34- peripheral blood monocytes (CD14+) were isolated using cellsorter followed by RNA extraction and hybridization on Affymetrix microarrays.