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Status |
Public on Jan 01, 2024 |
Title |
CD34+ monocyte subset is highly susceptible to HIV-1 infection |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
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.
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Contributor(s) |
Takahashi N, Noyori O, Eltalkhawy YM, Komohara Y, Nakayama H, Oka S, Takiguchi M, Suzu S |
Citation missing |
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Submission date |
Apr 10, 2023 |
Last update date |
Jan 01, 2024 |
Contact name |
Naofumi Takahashi |
Organization name |
Kumamoto University
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Street address |
2-2-1 Honjo, Chuo-ku
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City |
Kumamoto |
ZIP/Postal code |
8600811 |
Country |
Japan |
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Platforms (1) |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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Samples (2) |
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Relations |
BioProject |
PRJNA954042 |
Supplementary file |
Size |
Download |
File type/resource |
GSE229346_RAW.tar |
9.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
Processed data included within Sample table |
Processed data provided as supplementary file |
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