CD34+ monocyte subset is highly susceptible to HIV-1 infection
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ABSTRACT:
PROVIDER: PRJNA954042 | ENA |
REPOSITORIES: ENA
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Project description: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.
2024-01-01 | GSE229346 | GEO
Project description:Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. However, CD14++CD16+ monocytes remain the most poorly characterized subset so far. Therefore we analyzed the transcriptomes of the three monocyte subsets using SuperSAGE in combination with high-throughput sequencing. Analysis of 5,487,603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the two other monocyte subsets. CD14++CD16+ monocytes were linked to antigen processing and presentation (e.g. CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (e.g. TGFB1, AIF1, PTPN6), and to angiogenesis (e.g. TIE2, CD105). Therefore we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. Human monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) were isolated from 12 healthy volunteers based on MACS technology. Total RNA from monocyte subsets was isolated and same aliquots from each donor and monocyte subset were matched for SuperSAGE. Three SuperSAGE libraries (CD14++CD16-, CD14++CD16+ and CD14+CD16++) were generated.
2011-07-24 | E-GEOD-30811 | biostudies-arrayexpress
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